Crystal Structure of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, and an Fe$_4$S$_4$ Cluster

Formate dehydrogenase H from Escherichia coli contains selenocysteine (SeCys), molybdenum, two molybdopterin guanine dinucleotide (MGD) cofactors, and an Fe$_4$S$_4$ cluster at the active site and catalyzes the two-electron oxidation of formate to carbon dioxide. The crystal structures of the oxidized [Mo(VI), Fe$_4$S$_{4(ox)}$] form of formate dehydrogenase H (with and without bound inhibitor) and the reduced [Mo(IV), Fe$_4$S$_{4(red)}$] 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 SeCys$^{140}$ and His$^{141}$ in proton abstraction and the molybdenum, molybdopterin, Lys$^{44}$, and the Fe$_4$S$_4$ cluster in electron transfer.