CRYSTAL-STRUCTURE OF FORMATE DEHYDROGENASE-H - CATALYSIS INVOLVING MO, MOLYBDOPTERIN, SELENOCYSTEINE, AND AN FE4S4 CLUSTER

Formate dehydrogenase H from Escherichia coli contains selenocysteine (SeCys), molybdenum, two molybdopterin guanine dinucleotide (MGD) cofa ctors, and an Fe4S4 cluster at the active site and catalyzes the two-e lectron oxidation of formate to carbon dioxide. The crystal structures of the oxidized [Mo(VI), Fe4S4(ox)] form of formate dehydrogenase H ( with and without bound inhibitor) and the reduced [Mo(IV), Fe4S4(red)] form have been determined, revealing a four-domain alpha beta structu re with the molybdenum directly coordinated to selenium and both MGD c ofactors. These structures suggest a reaction mechanism that directly involves SeCys(140) and His(141) in proton abstraction and the molybde num, molybdopterin, Lys(44), and the Fe4S4 cluster in electron transfe r.