title: Crystal structure of formate dehydrogenase H: catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 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), 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 alphabeta 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.
authors.affiliation: Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Rockville, MD 20852, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Boyington
authors.forename: V N
authors.initials: VN
authors.lastname: Gladyshev
authors.forename: S V
authors.initials: SV
authors.lastname: Khangulov
authors.forename: T C
authors.initials: TC
authors.lastname: Stadtman
authors.forename: P D
authors.initials: PD
authors.lastname: Sun
mesh_terms: D001665:Binding Sites; D002245:Carbon Dioxide / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D004579:Electron Transport; D004926:Escherichia coli / Q000201:enzymology; D005296:Ferrous Compounds / Q000737:chemistry*; D005560:Formate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D005561:Formates / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D006864:Hydrogenase / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008982:Molybdenum / Q000737:chemistry / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D011622:Pterins / Q000737:chemistry / Q000378:metabolism; D017279:Selenocysteine / Q000737:chemistry / Q000378:metabolism
chemical_list: D005296:Ferrous Compounds; D005561:Formates; D006150:Guanine Nucleotides; D008024:Ligands; D009097:Multienzyme Complexes; D009573:Nitrites; D011522:Protons; D011622:Pterins; D017279:Selenocysteine; C030544:formic acid; C063761:molybdopterin guanine dinucleotide; D002245:Carbon Dioxide; D008982:Molybdenum; D006864:Hydrogenase; D005560:Formate Dehydrogenases; C054017:formate hydrogenlyase; C022597:ferrous sulfide