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Catalytic Site Atlas

CSA LITERATURE entry for 1aa6

E.C. nameformate dehydrogenase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.2.1.2
CSA Homologues of 1aa6
CSA Entries With UniProtID P07658
CSA Entries With EC Number 1.2.1.2
PDBe Entry 1aa6
PDBSum Entry 1aa6
MACiE Entry 1aa6

Literature Report

IntroductionFormate Dehydrogenase H (FDH-H) from E. coli is a 79kDa polypeptide component of the anaerobic formate hydrogen lyase complex. It catalyses the oxidation of formate to carbon dioxide with the release of a proton and two electrons.
MechansimInitially, formate binds to Mo 800 via one of its oxygens and displaces SeCys140. Formate is then oxidised to carbon dioxide. Two electrons are transferred to Mo800 reducing it from Mo(VI) to Mo(IV). The transfer of electrons from formate to Mo 800 may occur by direct two-electron transfer or by direct hydride transfer. The alpha proton of formate is transferred to SeCys140 and then to His141.
A selenium-carboxylated intermediate may be formed before CO2 is released.
Electrons from Mo(IV) are shuttled to the Fe4S4 cluster one at a time so an intermediate with Mo(V) and reduced Fe4S4 is produced. This is supported by evidence from electron paramagnetic resonance (EPR) experiments. Electron shuttling occurs by a ping pong mechanism through the partly delocalised ring of molybdopterin guanine dinucleotide (MGD) 802 and hydrogen bonds linking MGD, HOH 30, Lys44 and the Fe4S4 cluster. The Fe4S4 cluster is then oxidised by another electron acceptor. It is not known what functions as the final electron acceptor in vivo. Benzyl viologen (BV) has been used as the final electron acceptor in experiments. After Mo(V) is oxidised to Mo(IV) the proton on His141 can be released to the solvent.

Reaction

Catalytic Sites for 1aa6

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA4444macie:sideChainFacilitates electron transfer between HOH 30 and the Fe4S4 cluster.
CseA140140macie:sideChainAccepts the alpha proton from formate. A selenium-carboxylated intermediate may be formed on this residue during the oxidation of formate to CO2.
HisA141141macie:sideChainAfter the proton from formate is transferred to SeCys140 it is passed on to His141. Evidence from electron paramagnetic resonance also supports the protonation of His141 by the alpha proton of formate (PMID: 9036855).
ArgA333333macie:sideChainStabilises the free selenol on SeCys140 after it is displaced from Mo by the substrate.

Literature References

Notes:The crystal structure originally deposited and analysed by Boyington et al in PMID:9036855 has been revised by Raaijmakers and Romao in PMID:16830149. A section of the main chain, including two catalytically important residues SeCys140 and His141, was repositioned. The pdb structure contains the reduced form (MO(IV),FE4S4(RED)) of FDH-H. The oxidised form can be found in pdb 1fdo. The position of formate in it's binding site was modelled based on a a crystal structure of the oxidised enzyme with nitrite, an inhibitor, bound to Mo 800 as in pdb 1fdi.
Boyington JC
Crystal structure of formate dehydrogenase H: catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 cluster.
Science 1997 275 1305-1308
PubMed: 9036855
Raaijmakers HC
Formate-reduced E. coli formate dehydrogenase H: The reinterpretation of the crystal structure suggests a new reaction mechanism.
J Biol Inorg Chem 2006 11 849-854
PubMed: 16830149
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