Dalton Transactions

doi: 10.1039/b513879ppmid: N/A

doi: 10.1039/b513880apmid: N/A

doi: 10.1039/b513314apmid: 16234913

doi: 10.1039/b513687npmid: N/A

Mowat, Christopher G.; Chapman, Stephen K.

doi: 10.1039/b505184cpmid: 16234915

Heme is one of the most pervasive cofactors in nature and the c-type cytochromes represent one of the largest families of heme-containing proteins. Recent progress in bacterial genomic analysis has revealed a vast range of genes encoding novel c-type cytochromes that contain multiple numbers of heme cofactors. The genome sequence of , for example, includes some one hundred genes encoding c-type cytochromes, with around seventy of these containing two, or more, heme groups and with one protein containing an astonishing twenty seven heme groups. This wealth of cytochromes is of great significance in the respiratory flexibility shown by bacteria such as In addition, we are now discovering that many of these multi-heme cytochromes have associated enzymatic activities and in some cases this is revealing new chemistries. The purpose of this perspective is to describe recent progress in the structural and functional analyses of these new multi-heme cytochromes. To illustrate this we have chosen to focus on three of these cytochromes which exhibit catalytic activities; nitrite reductase, hydroxylamine oxidoreductase and tetrathionate reductase. In addition we consider the multi-heme cytochromes from and species. Finally, we consider and contrast the repeating structural modules found in these multi-heme cytochromes.

Lieberman, Raquel L.; Rosenzweig, Amy C.

doi: 10.1039/b506651dpmid: 16234916

Particulate methane monooxygenase is a copper-containing, membrane-bound metalloenzyme that converts methane to methanol in Nature. How pMMO accomplishes this difficult reaction under ambient conditions is one of the major unsolved problems in bioinorganic chemistry. Despite considerable research efforts in the past 20 years, the active site of the enzyme remains unknown. We recently solved the first crystal structure of pMMO to 2.8 Å resolution, revealing the overall structure, oligomerization state, subunit ratio, and composition and location of the metal centers. Almost none of the key structural features were predicted. In this Perspective, we review the state of knowledge before and after the structure determination, emphasizing elucidation of the pMMO active site.

Vincent, Kylie A.; Cracknell, James A.; Parkin, Alison; Armstrong, Fraser A.

doi: 10.1039/b508520apmid: 16234917

Hydrogenases provide an inspiration for future energy technologies. The active sites of these microbial enzymes contain Fe or Ni and Fe coordinated by CO and CN ligands: yet they have activities for hydrogen cycling that compare with Pt catalysts. Is there a future for enzymes in technological H cycling? There are obviously going to be disadvantages, perhaps overwhelming, as enzymes are notoriously fragile; yet what are the positive aspects and can we learn any chemistry that might be applied to produce the electrolytic and fuel cell catalysts of the future? We have developed a suite of novel electrochemical experiments to probe the chemistry of hydrogenases. The reactions are controlled and monitored at the surface of a small electrode, and characteristic catalytic properties are discernible from tiny amounts of sample material, so this approach can be used to search the microbial world for the best catalysts. Although electrochemistry does not provide structural information directly, it does give a “road map” by which to navigate the pathways and conditions that lead to particular states of the enzymes. This has prompted many interdisciplinary collaborations with other scientists who have provided microbiological, spectroscopic and structural contexts for this work. This article describes how these electrochemical experiments are set up, the data are analysed, and the results interpreted. We have determined mechanisms of catalysis, electron transfer, activation and inactivation, and defined important properties such as O tolerance and CO resistance in physical terms. Using an O-tolerant hydrogenase, we have demonstrated a “proof of concept” miniature fuel cell that will run on a mixed H/O feed in aqueous solution.

Mendel, Ralf R.

doi: 10.1039/b505527jpmid: 16234918

Molybdenum and tungsten are available to all organisms, with molybdenum having the far greater abundance and availability. Molybdenum occurs in a wide range of metalloenzymes in bacteria, fungi, algae, plants and animals, while tungsten was found to be essential only for a limited range of bacteria. In order to gain biological activity, molybdenum has to be complexed by a pterin compound, thus forming a molybdenum cofactor. In this article I will review the way that molybdenum takes from uptake into the cell, formation of the molybdenum cofactor and its storage, to the final modification of molybdenum cofactor and its insertion into apo-metalloenzymes.

Allen, James W. A.; Barker, Paul D.; Daltrop, Oliver; Stevens, Julie M.; Tomlinson, Esther J.; Sinha, Neeti; Sambongi, Yoshi; Ferguson, Stuart J.

doi: 10.1039/b508139bpmid: 16234919

This perspective seeks to discuss why biology often modifies the fundamental iron-protoporphyrin IX moiety that is the very versatile cofactor of many heme proteins. A very common modification is the attachment of this cofactor covalent bonds to two (or rarely one) sulfur atoms of cysteine residue side chains. This modification results in -type cytochromes, which have diverse structures and functions. The covalent bonds are made in different ways depending on the cell type. There is little understanding of the reasons for this complexity in assembly routes but proposals for the rationale behind the covalent modification are presented. In contrast to the widespread -type cytochromes, the heme is restricted to a single enzyme, the cytochrome nitrite reductase that catalyses the one-electron reduction of nitrite to nitric oxide. This is an extensively derivatised heme; a comparison is drawn with another type of respiratory nitrite reductase in which the active site is a -type heme, but the product ammonia.

Seward, Harriet E.; Girvan, Hazel M.; Munro, Andrew W.

doi: 10.1039/b505362ppmid: 16234920

Cytochromes P450 are a ubiquitous group of hemoproteins that perform vital cellular reactions in all lifeforms. Until recently, it was thought that P450s contained non-covalently bound heme. However, it was established that covalent linkage of the heme macrocycle occurs naturally in one major group of the P450 superfamily. The reaction involves heme linkage to a conserved amino acid and is autocatalytic, occurring as a consequence of P450 turnover. This finding presents opportunities to engineer biotechnologically important P450s to covalently link the heme, in order to stabilize cofactor binding and to enhance operational stability of these P450s. This opportunity has been taken in studies on two important bacterial P450s and has produced variants with intriguingly different properties. In this article we survey the developments in the field, the relationships with heme macrocycle ligations in other proteins and the important impact that recent studies of heme ligation have had on our general appreciation of P450 structure and mechanism.