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Binding of nucleotides by proteins
“Of outstanding interest” in the opinion of structural biologists. Authors of reviews in the Current Opinion series of journals select from the previous yeafs papers those they consider to be “of outstanding interest”. They justify each selection in a short ‘annotation’. Some of the selected references from the February 1992 issue of Current Opinion in Structural Biology, which covers Protein-Nucleic Acid Lnteractions as well as Folding and Binding, are listed below under the titles of the reviews.
Binding
of nucleotides
by proteins
by
Georg E. Schulz KNIGHTON
DR, ZHENG J, TEN EXCK IF,
XUONG N-H, TA~R
&NORD
VA,
SS, SOWAD%IJM: Crystal Struc-
ture of the Catalytic subunit of Cyclic Adenosine Monophosphatedependent Protein Kinase. Science 1591, 253407-414. This paper explains a vast amount of chemical data by
presenting, for the first time, a three-dimensional stmcture of a protein kinase.
Role of accessory proteins by George H. Lorimer
in protein
folding
KAUENJ, SPIXZFADEN C, Zm MGM, WIDER G, WIDMER I-I, W~HRICH K, WALKINSHAW MD: Structure of Human CycIophilin and its Binding Site for Cyclosporln A Determined by X-ray Crystallography and NMR Spectroscopy. Nature 1991, 353:276-279.
The three-dimensional structure of cyclophilin with a bound tetrapeptidyl substrate is reported. The active site is located on the outside of an eight-stranded p-barrel. The inhibitor cyclosporin A occupies the tetrapeptidebiding site. VAN DLMW GD, STANDAERTRF, KARPLusPA, SCHREIBER SL, CIARDY J: Atomic Structure of FKBP-FK506, an ImmunophiIi&mmunosuppressant
Complex. .~&ce
1991, 252~839-852. The three-dimensional structure of the enzyme-inhibitor complex to 1.7A resolution is reported. Conserved aromatic residues form a hydrophobic site for the inhibitor. The configuration of the amide bond of the inhibitor changes from cb to trans upon binding. A carbonyl-bindhg pocket accommodates the C-9 keto oxygen of PK506 in a manner that is consistent with the notion that PK506 is a ‘transition-state analog’, a twisted amide surrogate. The structure thus supports the ‘catalysis-by-distortion’ mechanism. HARDYSJS, RANIIAU LL A Kinetic Partitioning
Model of Sekctive Binding of Nonnative Proteins By the Bacterial Chaperone SecB. Sciarce 1991, 25 1:439-443.
An interesting model based upon kinetic partitioning between the pathways of folding and association with set B. The phenomenon of kinetic partitioning is more generally relevant to the interaction of unfolded proteins with Volume 2
other chaperones. It is demonstrated that secB binds avidly to the non-native states of structurally unrelated proteins. This provides a useful conceptual framework for considering the dynamics of protein secretion.
Number 2
1992
FIAHERTY KM,
MCKAY
DB,
KAENZH W,
HONES
KC:
Similarity
of the Three-dimensional Structures of Actin and the ATPase Fragment of a 70-kDa Heat Shock Cognate Protein. Pm Nat1 Acud Sci USA 1991,
88:5041-5045. An interesting comparison of two look-alike proteins. Obviously these proteins share structural and mechanistic unity at the ATPase site. Are there additional mechanistic parallels to be found?
Mutational analysis of protein stability Robert T. Sauer and Wendell A. Lim
by
RENNELLD, BOUVIERSE, HARDY LW, PO’IFETEARz Systematic Mutation of Bacteriophage Mol Biol 1991, 222:67+80.
T4 Lysozyme. J
A comprehensive study of the effects of over 2000 amino acid shbstitutions on the activity in uivo of T4 lysozyme. LLM WA, SAUERRT: The Role of Internal Packing Interactions in Determining the Structure and Stability of a Protein. J Mol Biol 191, 219:359-376.
A study showing that almost 70% of all combinations of Phe, Ile, Met, Leu and Val can be accommodated in a three-residue packing unit in the core of h repressor. DILL KA, SHOKIJE D: Denatured States of Proteins. Annu Rev Biocbem 1991, 60:795825. An excellent review of theory and experiments directed at understanding the denatured conformations of proteins.
Secondary-structure Oleg B. Ptitsyn
formation
and stability
by
PITISYN OB: How Does Protein Synthesis Give Rise to the 3D-Structure? EEiXYLett 1991, 285:176-181. A short review of recent work on the protein folding problem. A hypothesis is presented which may explain how protein can achieve its native three-dimensional structure in the face of an astronomically large number of possible. alternative conformations. 81
Binding
of nucleotides
by proteins
by
Georg E. Schulz KNIGHTON
DR, ZHENG J, TEN EXCK IF,
XUONG N-H, TA~R
&NORD
VA,
SS, SOWAD%IJM: Crystal Struc-
ture of the Catalytic subunit of Cyclic Adenosine Monophosphatedependent Protein Kinase. Science 1591, 253407-414. This paper explains a vast amount of chemical data by
presenting, for the first time, a three-dimensional stmcture of a protein kinase.
Role of accessory proteins by George H. Lorimer
in protein
folding
KAUENJ, SPIXZFADEN C, Zm MGM, WIDER G, WIDMER I-I, W~HRICH K, WALKINSHAW MD: Structure of Human CycIophilin and its Binding Site for Cyclosporln A Determined by X-ray Crystallography and NMR Spectroscopy. Nature 1991, 353:276-279.
The three-dimensional structure of cyclophilin with a bound tetrapeptidyl substrate is reported. The active site is located on the outside of an eight-stranded p-barrel. The inhibitor cyclosporin A occupies the tetrapeptidebiding site. VAN DLMW GD, STANDAERTRF, KARPLusPA, SCHREIBER SL, CIARDY J: Atomic Structure of FKBP-FK506, an ImmunophiIi&mmunosuppressant
Complex. .~&ce
1991, 252~839-852. The three-dimensional structure of the enzyme-inhibitor complex to 1.7A resolution is reported. Conserved aromatic residues form a hydrophobic site for the inhibitor. The configuration of the amide bond of the inhibitor changes from cb to trans upon binding. A carbonyl-bindhg pocket accommodates the C-9 keto oxygen of PK506 in a manner that is consistent with the notion that PK506 is a ‘transition-state analog’, a twisted amide surrogate. The structure thus supports the ‘catalysis-by-distortion’ mechanism. HARDYSJS, RANIIAU LL A Kinetic Partitioning
Model of Sekctive Binding of Nonnative Proteins By the Bacterial Chaperone SecB. Sciarce 1991, 25 1:439-443.
An interesting model based upon kinetic partitioning between the pathways of folding and association with set B. The phenomenon of kinetic partitioning is more generally relevant to the interaction of unfolded proteins with Volume 2
other chaperones. It is demonstrated that secB binds avidly to the non-native states of structurally unrelated proteins. This provides a useful conceptual framework for considering the dynamics of protein secretion.
Number 2
1992
FIAHERTY KM,
MCKAY
DB,
KAENZH W,
HONES
KC:
Similarity
of the Three-dimensional Structures of Actin and the ATPase Fragment of a 70-kDa Heat Shock Cognate Protein. Pm Nat1 Acud Sci USA 1991,
88:5041-5045. An interesting comparison of two look-alike proteins. Obviously these proteins share structural and mechanistic unity at the ATPase site. Are there additional mechanistic parallels to be found?
Mutational analysis of protein stability Robert T. Sauer and Wendell A. Lim
by
RENNELLD, BOUVIERSE, HARDY LW, PO’IFETEARz Systematic Mutation of Bacteriophage Mol Biol 1991, 222:67+80.
T4 Lysozyme. J
A comprehensive study of the effects of over 2000 amino acid shbstitutions on the activity in uivo of T4 lysozyme. LLM WA, SAUERRT: The Role of Internal Packing Interactions in Determining the Structure and Stability of a Protein. J Mol Biol 191, 219:359-376.
A study showing that almost 70% of all combinations of Phe, Ile, Met, Leu and Val can be accommodated in a three-residue packing unit in the core of h repressor. DILL KA, SHOKIJE D: Denatured States of Proteins. Annu Rev Biocbem 1991, 60:795825. An excellent review of theory and experiments directed at understanding the denatured conformations of proteins.
Secondary-structure Oleg B. Ptitsyn
formation
and stability
by
PITISYN OB: How Does Protein Synthesis Give Rise to the 3D-Structure? EEiXYLett 1991, 285:176-181. A short review of recent work on the protein folding problem. A hypothesis is presented which may explain how protein can achieve its native three-dimensional structure in the face of an astronomically large number of possible. alternative conformations. 81