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Editorial overview: Bioinorganic chemistry: Recent advances in bioinorganic chemistry
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ScienceDirect Editorial overview: Bioinorganic chemistry: Recent advances in bioinorganic chemistry Elizabeth M Nolan and Mitsuhiko Shionoya Current Opinion in Chemical Biology 2014, 19:vii–ix For a complete overview see the Issue 1367-5931/$ – see front matter, Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.cbpa.2014.03.016
Elizabeth M Nolan Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue 16-573B, Cambridge, MA 02139, USA e-mail: [email protected] Elizabeth M Nolan is an Assistant Professor in the Department of Chemistry at MIT. She received her bachelor’s degree from Smith College and her PhD from MIT, where she worked with Professor Stephen J Lippard. She was a NIH postdoctoral fellow with Professor Christopher T Walsh at Harvard Medical School. Her current research focuses on antimicrobial peptides and the homeostasis of metals in the context of the host/microbe interaction.
Mitsuhiko Shionoya Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan e-mail: [email protected] Mitsuhiko Shionoya is a Chemistry Professor at the Graduate School of Science, the University of Tokyo. His research focuses on bio-inspired supramolecular array, space, and motion (e.g. metallo-DNA and peptides, molecular machines, coordination capsules and cages, porous crystalline materials). He was appointed as Editor-in-Chief of Chemistry Letters in 2013.
www.sciencedirect.com
In this issue of Current Opinion in Chemical Biology, we present one dozen reviews that cover various facets in the broad field bioinorganic chemistry, including metalloprotein engineering, metals in medicine, the homeostasis of metals in the host/microbe interaction, and recent advances in our understanding of metalloenzymes and metallocofactors. Metalloprotein design and engineering is currently an active area of research and is highlighted by four reviews in this collection. Bos and Roelfes [1] summarize recent advances in the design, construction, and characterization of artificial metalloenzymes, as well as peptide-based and DNA-based systems, for enantioselective catalysis. These strategies have provided new routes for asymmetric transfer hydrogenation (ATH), olefin metathesis and C–H activation, and the application of an artificial ATHase in chemoenzymatic cascade reactions. By taking advantage of secondary sphere interactions afforded by protein scaffolds, some of the reactions presented in this work have no equivalent in conventional homogeneous catalysis or biocatalysis. Progress in the design of artificial metalloenzymes is also addressed by Du¨rrenberger and Ward [2] with particular emphasis on a variety of biohybrid catalysts reported recently. Different anchoring methods, which allow for incorporation of abiotic cofactors into biomolecules by covalent modification or supramolecular approaches, as well as strategies based on de novo design, are discussed in this review. There is great hope that such approaches may overcome some of the limitations encountered with both enzymes and traditional organometallic catalysts. Strategic modification of native metalloprotein scaffolds provides another opportunity for creating new metalloenzymes with desired reactivity. Lu and colleagues [3] review recent advances in rational metalloprotein design, including the incorporation of unnatural amino acids and unnatural metal cofactors, as well as library screening and directed evolution. Hybrid approaches that effectively combine both rational design and directed evolution to achieve more active or more interesting artificial metalloenzymes are also considered. Coordination chemistry is a powerful tool for creating new peptide and protein-based architectures, and Tezcan and colleagues [4] discuss recent progress in metal-mediated peptide and protein self assembly. This exciting sub-discipline combines the principles of inorganic coordination chemistry, protein design, and supramolecular chemistry to achieve artificial metallopeptide and -protein scaffolds with remarkable structural and functional diversity. Oohora and Hayashi [5] review timely efforts in the rational design of supramolecular hemoprotein assemblies. These assemblies exhibit a variety of structural attributes and may be divided into two general categories based on relative size: size-defined hemoprotein oligomers that form as a result of metal coordination between proteins or by domain swapping and larger hemoprotein fibrils, vesicles, or arrays. On the basis of the established physical and chemical properties of metalloporphyrins, the authors note that functional Current Opinion in Chemical Biology 2014, 19:vii–ix
viii Bioinorganic chemistry
hemoprotein assemblies may have practical utility in the development of smart biomaterials and biodevices. Two contributions to this collection highlight recent advances in medicinal inorganic chemistry. First, Do¨rr and Meggers [6] review the design and characterization of inert metal complexes that serve as protein binders. In such complexes, the metal ion serves a purely structural role and orients the ligands to provide shape complementary to a binding pocket on a target protein. Sandwich, half-sandwich, and octahedral d6-metal complexes are highly promising scaffolds for structural templates of protein binders as metal-based probes or drug candidates. It is expected that such inorganic and organometallic scaffolds will complement organic small molecules that act as protein binders and enzyme inhibitors, and enable the discovery of compounds with unprecedented biological activities. Bioinorganic chemistry plays a prominent role in the development of new metal-based anticancer agents. Since the discovery of the antitumor activity of cisplatin, a large number of metal-based anticancer agents have been characterized and evaluated in vitro and in vivo. Muhammad and Guo [7] review recent developments in this area and emphasize Pt(IV) prodrugs, polynuclear Pt(II) DNA-binding complexes, anti-metastatic Ru(II)/Ru(III) complexes, and Au(I)/Au(III) and Ti(IV) antitumor active complexes. Metal ions are required for all forms of life and two reviews focus on the importance of the homeostasis of transition metal ions in the host/pathogen interaction. Braymer and Giedroc [8] discuss recent advances in copper and zinc homeostasis in bacterial pathogens, including the molecular basis for Cu(I) and Zn(II) toxicity and a timely overview of the various players involved in the control of Cu(I) and Zn(II) speciation in cells and in the context of the host/pathogen interaction. These players include newly discovered bacterial copper-trafficking and zinc-trafficking proteins as well as the hostdefense protein calprotectin. Almost all microbial pathogens require iron for replication in the vertebrate host and therefore utilize a variety of mechanisms to obtain this essential nutrient. Bacterial pathogens such as Staphylococcus aureus and Mycobacterium tuberculosis sequester heme from the host to obtain nutrient iron. Five distinct bacterial heme uptake systems have been identified to date. Goulding and colleagues [9] describe structural and biochemical studies that provide new insights into heme uptake pathways employed by bacterial pathogens. Secreted proteins utilized for bacterial heme acquisition, the machineries involved in heme transport across the bacterial cell membrane(s), and mechanisms for heme degradation inside of the bacterial cell are discussed. Given the importance of iron acquisition in the vertebrate host, heme uptake pathways provide a potential antibacterial drug target. Current Opinion in Chemical Biology 2014, 19:vii–ix
This bioinorganic themed issue closes with three reviews on metalloenzymes and metallocofactors. Brown and Chang [10] discuss how soil bacteria use metalloenzyme-dependent radical pathways to break down the complex aromatic heteropolymer lignin, which can account for up to 30% of plant biomass, and describe how advances in DNA sequencing allow for new oxidative systems in lignin-reactive bacteria to be identified. This review sets the stage for future investigations aimed at deciphering how lignin degradation occurs in the environment at the molecular level. Cytochrome P450 nitric oxide reductase (P450nor) is employed by denitrifying fungi to detoxify nitric oxide (NO) and reduce this toxic metabolite to nitrous oxide (N2O). Lehnert and colleagues [11] explain how studies of synthetic model complexes of ferric heme-nitrosyls exhibiting varied axial donor ligands as well as DFT and QM/MM calculations provide insight into the mechanism of fungal cytochrome P450 nitric oxide reductase (P450nor). Lastly, iron sulfur (FeS) clusters are metallocofactors that participate in electron transport, catalysis, and redox sensing, and Bak and Elliott [12] discuss our current understanding of the properties and functions of FeS clusters that contain ligands other than cysteine. Canonical FeS clusters contain cysteine ligands, and FeS clusters that exhibit ‘alternative’ ligands such as histidine, aspartate, arginine, and threonine continue to be discovered. In this review, His-ligated FeS clusters involved in cellular iron homeostasis and electron transport are described. How the presence of an alternative ligand results in tuning of the FeS cluster redox potential and proton-coupled electron transfer (PCET) is also considered. We enjoyed editing this edition of Current Opinion in Chemical Biology and we would like to give a special thanks to all of the authors for their thoughtful contributions as well as the researchers who are currently advancing this exciting multidisciplinary field.
References 1.
Bos J, Roelfes G: Artificial metalloenzymes for enantioselective catalysis. Curr Opin Chem Biol 2014, 19:135-143.
2.
Du¨rrenberger M, Ward TR: Recent achievements in the design and engineering of artificial metalloenzymes. Curr Opin Chem Biol 2014, 19:99-106.
3.
Petrik ID, Liu J, Lu Y: Metalloenzyme design and engineering through strategic modifications of native protein scaffolds. Curr Opin Chem Biol 2014, 19:67-75.
4.
Sontz PA, Song WJ, Tezcan FA: Interfacial metal coordination in engineered protein and peptide assemblies. Curr Opin Chem Biol 2014, 19:42-49.
5.
Hayashi T, Oohora K: Hemoprotein-based supramolecular assembling systems. Curr Opin Chem Biol 2014, 19:154-161.
6.
Do¨rr M, Meggers E: Metal complexes as structural templates for targeting proteins. Curr Opin Chem Biol 2014, 19:76-81.
7.
Muhammad N, Guo Z: Metal-based anticancer chemotherapeutic agents. Curr Opin Chem Biol 2014, 19:144-153. www.sciencedirect.com
Editorial overview: Bioinorganic chemistry: Recent advances in bioinorganic chemistry Nolan and Shionoya ix
8.
Braymer JJ, Giedroc DP: Recent developments in copper and zinc homeostasis in bacterial pathogens. Curr Opin Chem Biol 2014, 19:56-66.
11. McQuarters AB, Wirgaue NE, Lehnert N: Model complexes of key intermediates in fungal cytochrome P450 nitric oxide reductase (P450nor). Curr Opin Chem Biol 2014, 19:82-89.
9.
Contreras H, Chim N, Credali A, Goulding CW: Heme uptake in bacterial pathogens. Curr Opin Chem Biol 2014, 19:34-41.
12. Bak DW, Elliott SJ: Alternative FeS cluster ligands: tuning redox potentials and chemistry. Curr Opin Chem Biol 2014, 19:50-58.
10. Brown ME, Chang MCY: Exploring bacterial lignin degradation. Curr Opin Chem Biol 2014, 19:1-7.
www.sciencedirect.com
Current Opinion in Chemical Biology 2014, 19:vii–ix
ScienceDirect Editorial overview: Bioinorganic chemistry: Recent advances in bioinorganic chemistry Elizabeth M Nolan and Mitsuhiko Shionoya Current Opinion in Chemical Biology 2014, 19:vii–ix For a complete overview see the Issue 1367-5931/$ – see front matter, Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.cbpa.2014.03.016
Elizabeth M Nolan Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue 16-573B, Cambridge, MA 02139, USA e-mail: [email protected] Elizabeth M Nolan is an Assistant Professor in the Department of Chemistry at MIT. She received her bachelor’s degree from Smith College and her PhD from MIT, where she worked with Professor Stephen J Lippard. She was a NIH postdoctoral fellow with Professor Christopher T Walsh at Harvard Medical School. Her current research focuses on antimicrobial peptides and the homeostasis of metals in the context of the host/microbe interaction.
Mitsuhiko Shionoya Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan e-mail: [email protected] Mitsuhiko Shionoya is a Chemistry Professor at the Graduate School of Science, the University of Tokyo. His research focuses on bio-inspired supramolecular array, space, and motion (e.g. metallo-DNA and peptides, molecular machines, coordination capsules and cages, porous crystalline materials). He was appointed as Editor-in-Chief of Chemistry Letters in 2013.
www.sciencedirect.com
In this issue of Current Opinion in Chemical Biology, we present one dozen reviews that cover various facets in the broad field bioinorganic chemistry, including metalloprotein engineering, metals in medicine, the homeostasis of metals in the host/microbe interaction, and recent advances in our understanding of metalloenzymes and metallocofactors. Metalloprotein design and engineering is currently an active area of research and is highlighted by four reviews in this collection. Bos and Roelfes [1] summarize recent advances in the design, construction, and characterization of artificial metalloenzymes, as well as peptide-based and DNA-based systems, for enantioselective catalysis. These strategies have provided new routes for asymmetric transfer hydrogenation (ATH), olefin metathesis and C–H activation, and the application of an artificial ATHase in chemoenzymatic cascade reactions. By taking advantage of secondary sphere interactions afforded by protein scaffolds, some of the reactions presented in this work have no equivalent in conventional homogeneous catalysis or biocatalysis. Progress in the design of artificial metalloenzymes is also addressed by Du¨rrenberger and Ward [2] with particular emphasis on a variety of biohybrid catalysts reported recently. Different anchoring methods, which allow for incorporation of abiotic cofactors into biomolecules by covalent modification or supramolecular approaches, as well as strategies based on de novo design, are discussed in this review. There is great hope that such approaches may overcome some of the limitations encountered with both enzymes and traditional organometallic catalysts. Strategic modification of native metalloprotein scaffolds provides another opportunity for creating new metalloenzymes with desired reactivity. Lu and colleagues [3] review recent advances in rational metalloprotein design, including the incorporation of unnatural amino acids and unnatural metal cofactors, as well as library screening and directed evolution. Hybrid approaches that effectively combine both rational design and directed evolution to achieve more active or more interesting artificial metalloenzymes are also considered. Coordination chemistry is a powerful tool for creating new peptide and protein-based architectures, and Tezcan and colleagues [4] discuss recent progress in metal-mediated peptide and protein self assembly. This exciting sub-discipline combines the principles of inorganic coordination chemistry, protein design, and supramolecular chemistry to achieve artificial metallopeptide and -protein scaffolds with remarkable structural and functional diversity. Oohora and Hayashi [5] review timely efforts in the rational design of supramolecular hemoprotein assemblies. These assemblies exhibit a variety of structural attributes and may be divided into two general categories based on relative size: size-defined hemoprotein oligomers that form as a result of metal coordination between proteins or by domain swapping and larger hemoprotein fibrils, vesicles, or arrays. On the basis of the established physical and chemical properties of metalloporphyrins, the authors note that functional Current Opinion in Chemical Biology 2014, 19:vii–ix
viii Bioinorganic chemistry
hemoprotein assemblies may have practical utility in the development of smart biomaterials and biodevices. Two contributions to this collection highlight recent advances in medicinal inorganic chemistry. First, Do¨rr and Meggers [6] review the design and characterization of inert metal complexes that serve as protein binders. In such complexes, the metal ion serves a purely structural role and orients the ligands to provide shape complementary to a binding pocket on a target protein. Sandwich, half-sandwich, and octahedral d6-metal complexes are highly promising scaffolds for structural templates of protein binders as metal-based probes or drug candidates. It is expected that such inorganic and organometallic scaffolds will complement organic small molecules that act as protein binders and enzyme inhibitors, and enable the discovery of compounds with unprecedented biological activities. Bioinorganic chemistry plays a prominent role in the development of new metal-based anticancer agents. Since the discovery of the antitumor activity of cisplatin, a large number of metal-based anticancer agents have been characterized and evaluated in vitro and in vivo. Muhammad and Guo [7] review recent developments in this area and emphasize Pt(IV) prodrugs, polynuclear Pt(II) DNA-binding complexes, anti-metastatic Ru(II)/Ru(III) complexes, and Au(I)/Au(III) and Ti(IV) antitumor active complexes. Metal ions are required for all forms of life and two reviews focus on the importance of the homeostasis of transition metal ions in the host/pathogen interaction. Braymer and Giedroc [8] discuss recent advances in copper and zinc homeostasis in bacterial pathogens, including the molecular basis for Cu(I) and Zn(II) toxicity and a timely overview of the various players involved in the control of Cu(I) and Zn(II) speciation in cells and in the context of the host/pathogen interaction. These players include newly discovered bacterial copper-trafficking and zinc-trafficking proteins as well as the hostdefense protein calprotectin. Almost all microbial pathogens require iron for replication in the vertebrate host and therefore utilize a variety of mechanisms to obtain this essential nutrient. Bacterial pathogens such as Staphylococcus aureus and Mycobacterium tuberculosis sequester heme from the host to obtain nutrient iron. Five distinct bacterial heme uptake systems have been identified to date. Goulding and colleagues [9] describe structural and biochemical studies that provide new insights into heme uptake pathways employed by bacterial pathogens. Secreted proteins utilized for bacterial heme acquisition, the machineries involved in heme transport across the bacterial cell membrane(s), and mechanisms for heme degradation inside of the bacterial cell are discussed. Given the importance of iron acquisition in the vertebrate host, heme uptake pathways provide a potential antibacterial drug target. Current Opinion in Chemical Biology 2014, 19:vii–ix
This bioinorganic themed issue closes with three reviews on metalloenzymes and metallocofactors. Brown and Chang [10] discuss how soil bacteria use metalloenzyme-dependent radical pathways to break down the complex aromatic heteropolymer lignin, which can account for up to 30% of plant biomass, and describe how advances in DNA sequencing allow for new oxidative systems in lignin-reactive bacteria to be identified. This review sets the stage for future investigations aimed at deciphering how lignin degradation occurs in the environment at the molecular level. Cytochrome P450 nitric oxide reductase (P450nor) is employed by denitrifying fungi to detoxify nitric oxide (NO) and reduce this toxic metabolite to nitrous oxide (N2O). Lehnert and colleagues [11] explain how studies of synthetic model complexes of ferric heme-nitrosyls exhibiting varied axial donor ligands as well as DFT and QM/MM calculations provide insight into the mechanism of fungal cytochrome P450 nitric oxide reductase (P450nor). Lastly, iron sulfur (FeS) clusters are metallocofactors that participate in electron transport, catalysis, and redox sensing, and Bak and Elliott [12] discuss our current understanding of the properties and functions of FeS clusters that contain ligands other than cysteine. Canonical FeS clusters contain cysteine ligands, and FeS clusters that exhibit ‘alternative’ ligands such as histidine, aspartate, arginine, and threonine continue to be discovered. In this review, His-ligated FeS clusters involved in cellular iron homeostasis and electron transport are described. How the presence of an alternative ligand results in tuning of the FeS cluster redox potential and proton-coupled electron transfer (PCET) is also considered. We enjoyed editing this edition of Current Opinion in Chemical Biology and we would like to give a special thanks to all of the authors for their thoughtful contributions as well as the researchers who are currently advancing this exciting multidisciplinary field.
References 1.
Bos J, Roelfes G: Artificial metalloenzymes for enantioselective catalysis. Curr Opin Chem Biol 2014, 19:135-143.
2.
Du¨rrenberger M, Ward TR: Recent achievements in the design and engineering of artificial metalloenzymes. Curr Opin Chem Biol 2014, 19:99-106.
3.
Petrik ID, Liu J, Lu Y: Metalloenzyme design and engineering through strategic modifications of native protein scaffolds. Curr Opin Chem Biol 2014, 19:67-75.
4.
Sontz PA, Song WJ, Tezcan FA: Interfacial metal coordination in engineered protein and peptide assemblies. Curr Opin Chem Biol 2014, 19:42-49.
5.
Hayashi T, Oohora K: Hemoprotein-based supramolecular assembling systems. Curr Opin Chem Biol 2014, 19:154-161.
6.
Do¨rr M, Meggers E: Metal complexes as structural templates for targeting proteins. Curr Opin Chem Biol 2014, 19:76-81.
7.
Muhammad N, Guo Z: Metal-based anticancer chemotherapeutic agents. Curr Opin Chem Biol 2014, 19:144-153. www.sciencedirect.com
Editorial overview: Bioinorganic chemistry: Recent advances in bioinorganic chemistry Nolan and Shionoya ix
8.
Braymer JJ, Giedroc DP: Recent developments in copper and zinc homeostasis in bacterial pathogens. Curr Opin Chem Biol 2014, 19:56-66.
11. McQuarters AB, Wirgaue NE, Lehnert N: Model complexes of key intermediates in fungal cytochrome P450 nitric oxide reductase (P450nor). Curr Opin Chem Biol 2014, 19:82-89.
9.
Contreras H, Chim N, Credali A, Goulding CW: Heme uptake in bacterial pathogens. Curr Opin Chem Biol 2014, 19:34-41.
12. Bak DW, Elliott SJ: Alternative FeS cluster ligands: tuning redox potentials and chemistry. Curr Opin Chem Biol 2014, 19:50-58.
10. Brown ME, Chang MCY: Exploring bacterial lignin degradation. Curr Opin Chem Biol 2014, 19:1-7.
www.sciencedirect.com
Current Opinion in Chemical Biology 2014, 19:vii–ix