Crystal Structure of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, and an Fe₄S₄ Cluster

Authors

Jeffrey C. Boyington, National Institutes of Health (NIH), Rockville, MD
Vadim Gladyshev, University of Nebraska-LincolnFollow
Sergei V. Khangulov, Princeton University, Princeton, NJ
Thressa C. Stadtman, National Institutes of Health (NIH), Rockville, MD
Peter D. Sun, National Institutes of Health (NIH), Rockville, MD

Date of this Version

May 2007

Comments

Published in SCIENCE - VOL. 275 - 28 FEBRUARY 1997. Copyright 1997. Permission to use. http://www.sciencemag.org

Abstract

Formate dehydrogenase H from Escherichia coli contains selenocysteine (SeCys), molybdenum, two molybdopterin guanine dinucleotide (MGD) cofactors, and an Fe₄S₄ cluster at the active site and catalyzes the two-electron oxidation of formate to carbon dioxide. The crystal structures of the oxidized [Mo( VI), Fe₄S_4(ox)] form of formate dehydrogenase H (with and without bound inhibitor) and the reduced [Mo(IV ), Fe₄S_4(red)] form have been determined, revealing a four-domain ab structure with the molybdenum directly coordinated to selenium and both MGD cofactors. These structures suggest a reaction mechanism that directly involves SeCys₁₄₀ and His₁₄₁ in proton abstraction and the molybdenum, molybdopterin, Lys₄₄, and the Fe₄S₄ cluster in electron transfer.