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

Document Type

Article

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.