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Contents volume 43 a history of biochemistry
ix
CONTENTS
VOLUME 43 A HISTORY OF B I O C H E M I S T R Y
Selected Topics in the History of Biochemistry Personal Recollections. VIII P r e f a c e t o V o l u m e 43 ................................................................. C o n t r i b u t o r s t o t h i s V o l u m e .................................................... C o n t e n t s ....................................................................................
V
vii ix
Chapter 1. My World Through Science b y MICHAEL SELA C h i l d h o o d ..................................................................................... M y Y e a r s i n R o u m a n i a .................................................................... I n Tel A v i v a n d J e r u s a l e m ............................................................... A g a i n i n E u r o p e ............................................................................ F a m i l y .......................................................................................... P r o t e i n s a n d P r o t e i n M o d e l s ........................................................... R i b o n u c l e a s e ................................................................................. B a c k t o I m m u n o l o g y : S y n t h e t i c A n t i g e n s ......................................... I n t e r l u d e w i t h P o l y m e r s a n d E n z y m e s .............................................. A g a i n B a c k t o I m m u n o l o g i c a l R e s e a r c h ........................................... A n t i b o d i e s .................................................................................... G e n e t i c C o n t r o l of I m m u n e R e s p o n s e ............................................... T h y m u s I n d e p e n d e n c e .................................................................... O n P e p t i d e E p i t o p e s ....................................................................... E a r l y S t u d i e s t o w a r d R e c e p t o r s ....................................................... S y n t h e t i c V a c c i n e s ......................................................................... A n t i b o d i e s a n d t h e i r D r u g C o n j u g a t e s a g a i n s t C a n c e r ....................... E r b B R e c e p t o r s ............................................................................. O t h e r S t u d i e s o n A n t i g e n s a n d A n t i b o d i e s .......................................
1 3 4 6 7 8 13 16 19 21 23 26 28 29 31 31 33 34 37
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The Odyssey of Copolymer 1 - Drug/Vaccine against Multiple Sclerosis .......................................................................... Beginnings of Copolymer 1 in Experimental Allergic Encephalomyelitis (EAE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Start with Teva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mode of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Other Studies on Cop 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Some Remarks Concerning Cop 1 in Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . New Uses of Copolymer 1 ................................................................ Neuroregeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prevention of Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . TherapeuticVaccines against Autoimmune Diseases .......................... A Candidate Drug/Vaccine against Myasthenia Gravis ....................... My P r e s i d e n c y of the Weizmann I n s t i t u t e ......................................... Some Advice Concerning M a n a g e m e n t ............................................. My Scientific Activities .................................................................. My Students, Postdocs, and Guests .................................................. Some Public Activities ................................................................... Some People t h a t have M e a n t a Lot to Me ......................................... Some Memorable Encounters .......................................................... Involvement with Industry .............................................................. In Israel besides Science ................................................................. M y Travels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . M y 70th B i r t h d a y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hobbies ........................................................................................ S o m e U s e f u l P r e c e p t s for t h e Young ( a n d Not-So-Young) S c i e n t i s t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Concluding Remarks ...................................................................... Postscriptum ................................................................................ References ....................................................................................
Chapter 2. Hemoglobin Kinetics b y QUENTIN
A
38 38 41 41 44 45 46 46 47 48 49 51 57 59 65 66 71 77 81 82 83 86 87 89 90 92 92
Retrospect
H. GIBSON
Abstract ....................................................................................... E a r l y Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Oxygen Equilibrium Curve ....................................................... Early Kinetic Studies - Hartridge and Roughton ............................... Continuous-Flow Development ........................................................ R e s i s t a n c e t o D i f f u s i o n i n t h e R e d Cell M e m b r a n e . . . . . . . . . . . . . . . . . . . . . . . . . . . .
101 101 109 113 120 121
CONTENTS C a r b o n d i o x i d e R e a c t i o n s a n d R e p l a c e m e n t of O x y g e n b y CO ............. D e v e l o p m e n t of S t o p p e d - F l o w A p p a r a t u s .......................................... R e v i s i t i n g t h e R e p l a c e m e n t R e a c t i o n ............................................... A d a i r P a r a m e t e r s for CO B i n d i n g .................................................... K i n e t i c s : R o u g h t o n a n d t h e A d a i r E q u a t i o n ...................................... R e a c t i o n s o f O x y g e n w i t h H b a n d S o m e P r o b l e m s .............................. L a s t F l o w E x p e r i m e n t s w i t h O x y g e n ................................................ F a r e w e l l t o R o u g h t o n ..................................................................... A n I t a l i a n V i s i t ............................................................................. F l a s h P h o t o l y s i s ............................................................................ S u b u n i t R e a c t i o n s a n d D i m e r s ........................................................ T h e T w o - S t a t e M o d e l ..................................................................... S u b u n i t s i n t h e R e p l a c e m e n t R e a c t i o n ............................................. T h e O x y g e n R e a c t i o n a n d t h e F l a s h l a m p - P u m p e d Dye L a s e r .............. G e m i n a t e R e c o m b i n a t i o n ............................................................... E n t e r M o l e c u l a r D y n a m i c s ............................................................. N o n m a m m a l i a n H e m o g l o b i n s ......................................................... S c a p h a r c a I n a e q u i v a l v i s ................................................................. C o n c l u d i n g R e m a r k s ...................................................................... A p p r o x i m a t e T i m e s o f M a j o r E v e n t s i n H e m o g l o b i n R e s e a r c h .............
xi 122 124 129 130 132 133 138 143 146 150 155 164 168 170 176 180 187 192 196 197
Chapter 3. From Reindeers to Synchrotrons: Personal Recollections
by CARL-IVAR BRANDI~N A b s t r a c t ....................................................................................... T h e F i r s t Years .............................................................................. A n I n o r g a n i c C h e m i s t i n U p p s a l a .................................................... I n C a m b r i d g e 1962-1963 ................................................................. B u i l d i n g u p a G r o u p i n S t r u c t u r a l Biology i n U p p s a l a ....................... A l c o h o l D e h y d r o g e n a s e .................................................................. T h i o r e d o x i n a n d G l u t a r e d o x i n ........................................................ T h e D a r k Side of P h o t o s y n t h e s i s ..................................................... A C h a p e r o n e for F i b r e F o r m a t i o n i n B a c t e r i a .................................... I n t r o d u c t i o n t o P r o t e i n S t r u c t u r e : A T e x t b o o k .................................. S t r u c t u r a l Biology a t S y n c h r o t r o n s .................................................. S c i e n c e Policy a n d A d v i c e ............................................................... E p i l o g u e ....................................................................................... A c k n o w l e d g m e n t s .......................................................................... E d i t o r ' s F o o t n o t e ........................................................................... R e f e r e n c e s ....................................................................................
199 200 202 206 209 213 218 219 224 226 229 235 237 240 240 241
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Chapter 4. The Way to Oleg Ptitsyn and Beyond
by HENRYK ( H E I N I )
EISENBERG
Introduction ................................................................................. Lev Davidovich L a n d a u .................................................................. N i k o l a i W l a d i m i r o v i c h T i m o f e e f f - R e s s o v s k y. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Trofim Denisovich Lysenko ............................................................. Leonid Isaakovich Mandelshtam ..................................................... M i k h a i l V. V o l k e n s h t e i n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Oleg B o r i s o v i c h P t i t s y n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Protein Folding and Unfolding ........................................................ W h a t A b o u t N u c l e i c Acids? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Postscript ..................................................................................... Acknowledgments .......................................................................... References ....................................................................................
243 247 249 252 254 256 259 262 266 270 271 271
Chapter 5. Peptides and the Enzymes that Release or Inactivate Them: A Short History of My Life and Work Entwined
by ERVIN G .
ERDOS
C e n t r a l E u r o p e a n d Two World Wars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T h e War Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A f t e r t h e War . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R e s e a r c h in Buda pest .................................................................... University of Munich Beginnings of a Research Career - Kallikreins and Kinins ...................................................... M e l l o n I n s t i t u t e , P i t t s b u r g h , PA: E a r l y P e p t i d e Research - Kininases, Esterases, and Rare Earth Ions ....................... U n i v e r s i t y o f O k l a h o m a (1963-73): P e p t i d a s e s , ACE, a n d S h o c k ........... Peptides and Shock ........................................................................ A Book, A Tree, A S o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prolylcarboxypeptidase .................................................................. Carboxypeptidase N ...................................................................... ACE, K i n i n a s e II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Shock ........................................................................................... U n i v e r s i t y o f Texas S o u t h w e s t e r n M e d i c a l S c h o o l i n D a l l a s (1973-85): F u r t h e r Adventures with ACE ......................................................... ACE Inhibitors .............................................................................. Substance P ..................................................................................
279 283 287 288 289 295 301 308 309 310 312 312 314 314 316 318
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Expansion of Research at Home and Abroad ..................................... Carboxypeptidase N ...................................................................... ACE ............................................................................................. K a l l i k r e i n .................................................................................... Neprilysin ..................................................................................... University of Illinois at Chicago (1985- Present) Peptidases and Intimate Relationships between Receptors and Enzyme Inhibitors ...... K a l l i k r e i n .................................................................................... B1 Receptor ................................................................................... Deamidase .................................................................................... Carboxypeptidases N and M ........................................................... J u s t a Bit of Bragging .................................................................... Epilogue: Blurred Retrospect but Clear Hindsight ............................. Acknowledgments .......................................................................... Appendix ...................................................................................... References ....................................................................................
319 321 322 322 323 325 331 332 334 335 336 337 344 344 345
Chapter 6. Establishment of the Concept that Cancer is a Disease of DNA: Serendipitous Discoveries in My Research Career Concerning the Science of Carcinogenesis
by TAKASHI SUGIMURA Abstract ....................................................................................... Brief Background to Choosing a Career as a Scientist ........................ Discovery of the Carcinogenicity of 4-Nitroquinoline 1-oxide .............. Experience in the US ..................................................................... Carcinogenicity of N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) ................................ Discovery of AF-2, Furyl Nitrofuryl Acrylamide: A Food Preservative as a Mutagen and Carcinogen and Lessons from Microbial Testing ...... Mutagens/Carcinogens Produced in Cooking Meat/Fish under Ordinary Conditions ............................................. Discovery of Poly(ADP-ribose) and Poly(ADP-ribose) Polymerase ........ New Tu m o r Promoters other t h a n TPA ............................................. Dysdifferentiation in Precancerous and Cancerous Tissues ......................................................................... A n a l b u m i n e m i c Rats and Splicing M e c h a n i s m Change ...................... Pierisin, an Apoptogenic and Mutagenic Peptide, from Cabbage Butterfly .................................................................. Recollections and the Future ..........................................................
355 356 358 361 363 365 366 371 374 376 378 380 383
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Acknowledgments.......................................................................... References ....................................................................................
384 384
Chapter 7. The Tribulations of a Stateless European Child in His Discovery of America and His Thorny Path to Protein Thermodynamics by SERGEN. TIMASHEFF Origins ......................................................................................... " L i t t l e Russia" i n P a r i s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Insertion into French Society .......................................................... War: "Drole de G u e r r e " . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S a i l i n g away t o t h e U S A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Clash of Civilizations". .................................................................. The Jesuits ................................................................................... From E n g i n e e r i n g to Physics to Chemistry ....................................... G r a d u a t e School: F. F. N o r d . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Solving the Wrong Problem ............................................................. Kirkwood: Caltech,Yale ................................................................. W o r k i n g for t h e G o v e r n m e n t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I am a USDA Bureaucrat in Rome .................................................... S t r a s b o u r g , S a d r o n , S m a l l - A n g l e X-ray S c a t t e r i n g . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Back to Philadelphia: Solvent Interactions ........................................ I Become an Academic: Brandeis ..................................................... Jeffries Wyman .............................................................................. Two E n c o u n t e r s at Santa M a r g h e r i t a Ligure .................................... Behind the Iron Curtain ................................................................. My Talented Postdoctorals .............................................................. Tubulin, Double Rings, and Microtubules ......................................... Protein-Solvent Interactions: The Exclusion Principle ....................... Interaction of Tubulin with Antimitotic Drugs .................................. T h e F i n a l Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Retirement, Epilogue ..................................................................... References ....................................................................................
393 396 400 402 405 409 412 416 419 421 422 430 433 435 439 440 442 445 449 451 457 465 471 476 481 489
Chapter 8. Yeast Transport-ATPases and the Genome-sequencing Project by ANDREGOFFEAU My T r a i n i n g .................................................................................. My Laboratory FYSA .....................................................................
494 499
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xv
M y R e s e a r c h ................................................................................. T h e F1 M u t a n t s ............................................................................. T h e D i u r o n - r e s i s t a n t C y t o c h r o m e b M u t a n t s .................................... The Proton-translocating Plasma Membrane A T P a s e P m a l p ............................................................................... T h e M u l t i d r u g - e f f l u x A T P a s e P d r 5 p ................................................. M y H i d d e n A d m i n i s t r a t i v e Life ....................................................... T h e L a u n c h i n g o f C h r o m o s o m e III S e q u e n c i n g ................................. T h e L e s s o n s f r o m S e q u e n c i n g C h r o m o s o m e I I I .................................. T h e S e q u e n c i n g o f t h e o t h e r C h r o m o s o m e s ....................................... T h e S p e c i a l Role o f P i o t r S l o n i m s k i ................................................. E p i l o g u e ....................................................................................... R e f e r e n c e s .................................................................................... N a m e I n d e x ..................................................................................
502 502 504 505 511 514 516 522 525 528 530 532 537
CONTENTS
VOLUME 43 A HISTORY OF B I O C H E M I S T R Y
Selected Topics in the History of Biochemistry Personal Recollections. VIII P r e f a c e t o V o l u m e 43 ................................................................. C o n t r i b u t o r s t o t h i s V o l u m e .................................................... C o n t e n t s ....................................................................................
V
vii ix
Chapter 1. My World Through Science b y MICHAEL SELA C h i l d h o o d ..................................................................................... M y Y e a r s i n R o u m a n i a .................................................................... I n Tel A v i v a n d J e r u s a l e m ............................................................... A g a i n i n E u r o p e ............................................................................ F a m i l y .......................................................................................... P r o t e i n s a n d P r o t e i n M o d e l s ........................................................... R i b o n u c l e a s e ................................................................................. B a c k t o I m m u n o l o g y : S y n t h e t i c A n t i g e n s ......................................... I n t e r l u d e w i t h P o l y m e r s a n d E n z y m e s .............................................. A g a i n B a c k t o I m m u n o l o g i c a l R e s e a r c h ........................................... A n t i b o d i e s .................................................................................... G e n e t i c C o n t r o l of I m m u n e R e s p o n s e ............................................... T h y m u s I n d e p e n d e n c e .................................................................... O n P e p t i d e E p i t o p e s ....................................................................... E a r l y S t u d i e s t o w a r d R e c e p t o r s ....................................................... S y n t h e t i c V a c c i n e s ......................................................................... A n t i b o d i e s a n d t h e i r D r u g C o n j u g a t e s a g a i n s t C a n c e r ....................... E r b B R e c e p t o r s ............................................................................. O t h e r S t u d i e s o n A n t i g e n s a n d A n t i b o d i e s .......................................
1 3 4 6 7 8 13 16 19 21 23 26 28 29 31 31 33 34 37
x
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The Odyssey of Copolymer 1 - Drug/Vaccine against Multiple Sclerosis .......................................................................... Beginnings of Copolymer 1 in Experimental Allergic Encephalomyelitis (EAE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Start with Teva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mode of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Other Studies on Cop 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Some Remarks Concerning Cop 1 in Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . New Uses of Copolymer 1 ................................................................ Neuroregeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prevention of Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . TherapeuticVaccines against Autoimmune Diseases .......................... A Candidate Drug/Vaccine against Myasthenia Gravis ....................... My P r e s i d e n c y of the Weizmann I n s t i t u t e ......................................... Some Advice Concerning M a n a g e m e n t ............................................. My Scientific Activities .................................................................. My Students, Postdocs, and Guests .................................................. Some Public Activities ................................................................... Some People t h a t have M e a n t a Lot to Me ......................................... Some Memorable Encounters .......................................................... Involvement with Industry .............................................................. In Israel besides Science ................................................................. M y Travels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . M y 70th B i r t h d a y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hobbies ........................................................................................ S o m e U s e f u l P r e c e p t s for t h e Young ( a n d Not-So-Young) S c i e n t i s t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Concluding Remarks ...................................................................... Postscriptum ................................................................................ References ....................................................................................
Chapter 2. Hemoglobin Kinetics b y QUENTIN
A
38 38 41 41 44 45 46 46 47 48 49 51 57 59 65 66 71 77 81 82 83 86 87 89 90 92 92
Retrospect
H. GIBSON
Abstract ....................................................................................... E a r l y Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Oxygen Equilibrium Curve ....................................................... Early Kinetic Studies - Hartridge and Roughton ............................... Continuous-Flow Development ........................................................ R e s i s t a n c e t o D i f f u s i o n i n t h e R e d Cell M e m b r a n e . . . . . . . . . . . . . . . . . . . . . . . . . . . .
101 101 109 113 120 121
CONTENTS C a r b o n d i o x i d e R e a c t i o n s a n d R e p l a c e m e n t of O x y g e n b y CO ............. D e v e l o p m e n t of S t o p p e d - F l o w A p p a r a t u s .......................................... R e v i s i t i n g t h e R e p l a c e m e n t R e a c t i o n ............................................... A d a i r P a r a m e t e r s for CO B i n d i n g .................................................... K i n e t i c s : R o u g h t o n a n d t h e A d a i r E q u a t i o n ...................................... R e a c t i o n s o f O x y g e n w i t h H b a n d S o m e P r o b l e m s .............................. L a s t F l o w E x p e r i m e n t s w i t h O x y g e n ................................................ F a r e w e l l t o R o u g h t o n ..................................................................... A n I t a l i a n V i s i t ............................................................................. F l a s h P h o t o l y s i s ............................................................................ S u b u n i t R e a c t i o n s a n d D i m e r s ........................................................ T h e T w o - S t a t e M o d e l ..................................................................... S u b u n i t s i n t h e R e p l a c e m e n t R e a c t i o n ............................................. T h e O x y g e n R e a c t i o n a n d t h e F l a s h l a m p - P u m p e d Dye L a s e r .............. G e m i n a t e R e c o m b i n a t i o n ............................................................... E n t e r M o l e c u l a r D y n a m i c s ............................................................. N o n m a m m a l i a n H e m o g l o b i n s ......................................................... S c a p h a r c a I n a e q u i v a l v i s ................................................................. C o n c l u d i n g R e m a r k s ...................................................................... A p p r o x i m a t e T i m e s o f M a j o r E v e n t s i n H e m o g l o b i n R e s e a r c h .............
xi 122 124 129 130 132 133 138 143 146 150 155 164 168 170 176 180 187 192 196 197
Chapter 3. From Reindeers to Synchrotrons: Personal Recollections
by CARL-IVAR BRANDI~N A b s t r a c t ....................................................................................... T h e F i r s t Years .............................................................................. A n I n o r g a n i c C h e m i s t i n U p p s a l a .................................................... I n C a m b r i d g e 1962-1963 ................................................................. B u i l d i n g u p a G r o u p i n S t r u c t u r a l Biology i n U p p s a l a ....................... A l c o h o l D e h y d r o g e n a s e .................................................................. T h i o r e d o x i n a n d G l u t a r e d o x i n ........................................................ T h e D a r k Side of P h o t o s y n t h e s i s ..................................................... A C h a p e r o n e for F i b r e F o r m a t i o n i n B a c t e r i a .................................... I n t r o d u c t i o n t o P r o t e i n S t r u c t u r e : A T e x t b o o k .................................. S t r u c t u r a l Biology a t S y n c h r o t r o n s .................................................. S c i e n c e Policy a n d A d v i c e ............................................................... E p i l o g u e ....................................................................................... A c k n o w l e d g m e n t s .......................................................................... E d i t o r ' s F o o t n o t e ........................................................................... R e f e r e n c e s ....................................................................................
199 200 202 206 209 213 218 219 224 226 229 235 237 240 240 241
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Chapter 4. The Way to Oleg Ptitsyn and Beyond
by HENRYK ( H E I N I )
EISENBERG
Introduction ................................................................................. Lev Davidovich L a n d a u .................................................................. N i k o l a i W l a d i m i r o v i c h T i m o f e e f f - R e s s o v s k y. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Trofim Denisovich Lysenko ............................................................. Leonid Isaakovich Mandelshtam ..................................................... M i k h a i l V. V o l k e n s h t e i n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Oleg B o r i s o v i c h P t i t s y n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Protein Folding and Unfolding ........................................................ W h a t A b o u t N u c l e i c Acids? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Postscript ..................................................................................... Acknowledgments .......................................................................... References ....................................................................................
243 247 249 252 254 256 259 262 266 270 271 271
Chapter 5. Peptides and the Enzymes that Release or Inactivate Them: A Short History of My Life and Work Entwined
by ERVIN G .
ERDOS
C e n t r a l E u r o p e a n d Two World Wars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T h e War Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A f t e r t h e War . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R e s e a r c h in Buda pest .................................................................... University of Munich Beginnings of a Research Career - Kallikreins and Kinins ...................................................... M e l l o n I n s t i t u t e , P i t t s b u r g h , PA: E a r l y P e p t i d e Research - Kininases, Esterases, and Rare Earth Ions ....................... U n i v e r s i t y o f O k l a h o m a (1963-73): P e p t i d a s e s , ACE, a n d S h o c k ........... Peptides and Shock ........................................................................ A Book, A Tree, A S o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prolylcarboxypeptidase .................................................................. Carboxypeptidase N ...................................................................... ACE, K i n i n a s e II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Shock ........................................................................................... U n i v e r s i t y o f Texas S o u t h w e s t e r n M e d i c a l S c h o o l i n D a l l a s (1973-85): F u r t h e r Adventures with ACE ......................................................... ACE Inhibitors .............................................................................. Substance P ..................................................................................
279 283 287 288 289 295 301 308 309 310 312 312 314 314 316 318
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Expansion of Research at Home and Abroad ..................................... Carboxypeptidase N ...................................................................... ACE ............................................................................................. K a l l i k r e i n .................................................................................... Neprilysin ..................................................................................... University of Illinois at Chicago (1985- Present) Peptidases and Intimate Relationships between Receptors and Enzyme Inhibitors ...... K a l l i k r e i n .................................................................................... B1 Receptor ................................................................................... Deamidase .................................................................................... Carboxypeptidases N and M ........................................................... J u s t a Bit of Bragging .................................................................... Epilogue: Blurred Retrospect but Clear Hindsight ............................. Acknowledgments .......................................................................... Appendix ...................................................................................... References ....................................................................................
319 321 322 322 323 325 331 332 334 335 336 337 344 344 345
Chapter 6. Establishment of the Concept that Cancer is a Disease of DNA: Serendipitous Discoveries in My Research Career Concerning the Science of Carcinogenesis
by TAKASHI SUGIMURA Abstract ....................................................................................... Brief Background to Choosing a Career as a Scientist ........................ Discovery of the Carcinogenicity of 4-Nitroquinoline 1-oxide .............. Experience in the US ..................................................................... Carcinogenicity of N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) ................................ Discovery of AF-2, Furyl Nitrofuryl Acrylamide: A Food Preservative as a Mutagen and Carcinogen and Lessons from Microbial Testing ...... Mutagens/Carcinogens Produced in Cooking Meat/Fish under Ordinary Conditions ............................................. Discovery of Poly(ADP-ribose) and Poly(ADP-ribose) Polymerase ........ New Tu m o r Promoters other t h a n TPA ............................................. Dysdifferentiation in Precancerous and Cancerous Tissues ......................................................................... A n a l b u m i n e m i c Rats and Splicing M e c h a n i s m Change ...................... Pierisin, an Apoptogenic and Mutagenic Peptide, from Cabbage Butterfly .................................................................. Recollections and the Future ..........................................................
355 356 358 361 363 365 366 371 374 376 378 380 383
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Acknowledgments.......................................................................... References ....................................................................................
384 384
Chapter 7. The Tribulations of a Stateless European Child in His Discovery of America and His Thorny Path to Protein Thermodynamics by SERGEN. TIMASHEFF Origins ......................................................................................... " L i t t l e Russia" i n P a r i s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Insertion into French Society .......................................................... War: "Drole de G u e r r e " . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S a i l i n g away t o t h e U S A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Clash of Civilizations". .................................................................. The Jesuits ................................................................................... From E n g i n e e r i n g to Physics to Chemistry ....................................... G r a d u a t e School: F. F. N o r d . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Solving the Wrong Problem ............................................................. Kirkwood: Caltech,Yale ................................................................. W o r k i n g for t h e G o v e r n m e n t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I am a USDA Bureaucrat in Rome .................................................... S t r a s b o u r g , S a d r o n , S m a l l - A n g l e X-ray S c a t t e r i n g . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Back to Philadelphia: Solvent Interactions ........................................ I Become an Academic: Brandeis ..................................................... Jeffries Wyman .............................................................................. Two E n c o u n t e r s at Santa M a r g h e r i t a Ligure .................................... Behind the Iron Curtain ................................................................. My Talented Postdoctorals .............................................................. Tubulin, Double Rings, and Microtubules ......................................... Protein-Solvent Interactions: The Exclusion Principle ....................... Interaction of Tubulin with Antimitotic Drugs .................................. T h e F i n a l Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Retirement, Epilogue ..................................................................... References ....................................................................................
393 396 400 402 405 409 412 416 419 421 422 430 433 435 439 440 442 445 449 451 457 465 471 476 481 489
Chapter 8. Yeast Transport-ATPases and the Genome-sequencing Project by ANDREGOFFEAU My T r a i n i n g .................................................................................. My Laboratory FYSA .....................................................................
494 499
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M y R e s e a r c h ................................................................................. T h e F1 M u t a n t s ............................................................................. T h e D i u r o n - r e s i s t a n t C y t o c h r o m e b M u t a n t s .................................... The Proton-translocating Plasma Membrane A T P a s e P m a l p ............................................................................... T h e M u l t i d r u g - e f f l u x A T P a s e P d r 5 p ................................................. M y H i d d e n A d m i n i s t r a t i v e Life ....................................................... T h e L a u n c h i n g o f C h r o m o s o m e III S e q u e n c i n g ................................. T h e L e s s o n s f r o m S e q u e n c i n g C h r o m o s o m e I I I .................................. T h e S e q u e n c i n g o f t h e o t h e r C h r o m o s o m e s ....................................... T h e S p e c i a l Role o f P i o t r S l o n i m s k i ................................................. E p i l o g u e ....................................................................................... R e f e r e n c e s .................................................................................... N a m e I n d e x ..................................................................................
502 502 504 505 511 514 516 522 525 528 530 532 537