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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1fcb

E.C. nameL-lactate dehydrogenase (cytochrome)
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz)
CSA Homologues of 1fcbThere are 30 Homologs
CSA Entries With UniProtID P00175
CSA Entries With EC Number
PDBe Entry 1fcb
PDBSum Entry 1fcb
MACiE Entry M0102

Literature Report

IntroductionThe flavo-cytochrome enzyme is a lactate dehydrogenase that catalyses the transfer of a hydride equivalent from its hydroxy acid substrate to the enzyme bound flavin, and thence to proteins of the mitochondrial electron transport chain via a bound cytochrome. The enzyme contains two domains, the flavin domain, capable of converting lactate to pyruvate by itself, and the heme domain which contains the prosthetic group involved in electron transfer from the reduced flavin to an acceptor cytochrome.
MechansimThe enzyme catalyses the oxidation of lactate to pyruvate. In the wild type enzyme the OH and CH bond cleavages in lactate are highly asynchronous. The lactate hydroxyl proton is abstracted by His 373 to form the alkoxide either early in the reaction or in a pre-equilibrium. The developing charge on the oxygen is stabilised by Tyr254. The hydride is then transferred to the flavin, forming pyruvate.

Catalytic Sites for 1fcb

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA373453macie:sideChainThe residue acts as a base towards the lactate hydroxyl, forming an alkoxide which then drives the transfer of the alpha hydrogen to the flavin cofactor.
AspA282362macie:sideChainElectrostatic interactions between Asp282 and the general base His373 orientates the residue towards the substrate.
TyrA254334macie:sideChainThe residue's phenolic hydroxy group hydrogen bonds to the substrate alkoxide anion, lowering the intermediate's energy, and so facilitating its formation.

Literature References

Tsai CL
Mechanistic and structural studies of H373Q flavocytochrome b2: effects of mutating the active site base.
Biochemistry 2007 46 7844-7851
PubMed: 17563122
Brown BD
Endonucleolytic cleavage of a maternal homeo box mRNA in Xenopus oocytes.
Genes Dev 1990 4 1925-1935
PubMed: 1980477