Crystal Structure of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, and an Fe 4 S 4 Cluster

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 αβ 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.