Great Metalloclusters in Enzymology

Abstract

Key Words metalloproteins, iron-sulfur clusters, nitrogenase, hydrogenase, carbon monoxide dehydrogenase, nitrous oxide reductase f Abstract Metallocluster-containing enzymes catalyze some of the most basic redox transformations in the biosphere. The reactions catalyzed by these enzymes typically involve small molecules such as N 2 , CO, and H 2 that are used to generate both chemical building blocks and energy for metabolic purposes. During the past decade, structures have been established for the iron-sulfur-based metalloclusters present in the molybdenum nitrogenase, the iron-only hydrogenase, and the nickel-carbon monoxide dehydrogenase, and for the coppersulfide-based cluster in nitrous oxide reductase. Although these clusters are built from interactions observed in simpler metalloproteins, they contain novel features that may be relevant for their catalytic function. The mechanisms of metallocluster-containing enzymes are still poorly defined and represent substantial and continuing challenges to biochemists, biophysicists, and synthetic chemists. These proteins also provide a window into the union of the biological and inorganic worlds that may have been relevant to the early evolution of biochemical catalysis. Annu. Rev. Biochem. 2002. 71:221-46 DOI: 10.1146 Copyright © 2002 by Annual Reviews. All rights reserved 221 0066-4154/02/0707-0221$14.00 Annu. Rev. Biochem. 2002.71:221-246 CONTENTS INTRODUCTIONAmong the most remarkable chemical transformations in biological systems are the oxidation-reduction reactions of some of the smallest molecules, including N 2 , CO, and H 2 . Redox processes involving these species not only generate basic chemical building blocks required by living organisms but can also generate the energy needed to fuel their metabolisms. Although binding sites of exquisite specificity for molecules ranging from small organic metabolites to enormous macromolecules can be constructed from the standard amino acids and nucleotides, these groups are poorly suited for binding and catalyzing the redox reactions of diatomic and similar molecules. Consequently, it is necessary to incorporate specialized metallocofactors into enzymes to provide the binding interactions for these small substrates, as well as to confer the catalytic capabilities necessary to achieve the desired transformations. Metalloclusters also provide a fascinating window into the union of the biological and inorganic worlds that may have arisen early in evolution to effect the metabolism of small molecules required to drive the energetic and growth needs of primitive organisms. Indeed, it has been proposed that before an RNA world could even exist, the central biochemical processes arose from a surface-based metabolism on the iron-sulfur-containing mineral pyrite (1). What may be the vestiges of this metabolism can perhaps still be perceived in these contemporary clusters.This review surveys the metalloclusters that have been structurally characterized in enzymes (Figure 1). Although the choice of clusters covered is partl...

Nitrate reduction and the nitrogen cycle in archaea

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CO-Sensing Mechanisms

“…As a result, some 2,000 non-fire-related CO-poisoning deaths occur annually in the United States (92). Human toxicity is attributed to the high affinity of CO for iron such that the oxygen capacity of hemoglobin is reduced, and the gas is broadly inhibitory for heme proteins and nonheme iron enzymes including hydrogenase (2,45,106) and nitrogenase (20,83,106). In light of its heme affinity, it is a biological irony that the primary endogenous source of CO in mammals is heme degradation catalyzed by multiple heme oxygenase activities in the cell.…”

Flavodoxin hydroquinone reduces Azotobacter vinelandii Fe protein to the all-ferrous redox state with a S = 0 spin state

“…The discovery (4) and characterization (5)(6)(7)(8)(9)(10)(11)(12) of an [Fe 4 S 4 ] 0 Av2 has raised questions regarding how nitrogenase functions (13)(14)(15) because the 2ϩ͞0 couple involves two electrons instead of one (5)(6)(7) to decrease the optimal ATP requirement 2-fold. This energy efficiency makes the study of [Fe 4 (17), and an E m ϭ -790 mV (18) was estimated for the 1ϩ͞0 couple, which is in line with E m estimates of all-ferrous Fe-S clusters by using discrete Fourier transform calculations (19).…”