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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1bwl

E.C. nameNADPH dehydrogenase
SpeciesCandida albicans (Yeast)
E.C. Number (IntEnz) 1.6.99.1
CSA Homologues of 1bwl
CSA Entries With UniProtID Q02899
CSA Entries With EC Number 1.6.99.1
PDBe Entry 1bwl
PDBSum Entry 1bwl
MACiE Entry M0319

Literature Report

IntroductionOld yellow enzyme (OYE), isolated from Candida albicans, is a NADPH oxidoreductase. Its FMN cofactor is reduced by NADPH, and in turn goes on to reduce the substrate. The exact physiological substrate(s) of OYE are yet to be confirmed, though it is known to act on molecular oxygen, alpha,beta-unsaturated ketones and aldehydes, and quinones. OYE is thought to be involved in general detoxification within the cell.
MechansimThis mechanism describes the reduction of an alpha,beta-unsaturated ketone.
NADPH transfers a hydride from C4 to the si face of the N5 position of FMN, reducing it and causing a negative charge to build up on N1. Reduced FMN then transfers a hydride from the N5 position to the beta-carbon of the substrate, forming an enolate intermediate that is stabilised by His191, Arg194 and Tyr196. The carbonyl reforms and the alpha-carbon is protonated by Tyr196 to form the saturated carbonyl product.

Catalytic Sites for 1bwl

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnA191192macie:sideChainHis191 polarises the carbonyl bond of the substrate, thus making alpha,beta-unsaturated ketone more electrophilic. It also stabilises the enolate intermediate by hydrogen bonding to the negatively charged oxygen.
ThrA3738macie:sideChainThr37 decreases the redox potential of the FMN cofactor by hydrogen bonding to the C4 carbonyl.
HisA194195macie:sideChainAsn194 polarises the carbonyl bond of the substrate, thus making alpha,beta-unsaturated ketone more electrophilic. It also stabilises the enolate intermediate by hydrogen bonding to the negatively charged oxygen.
TyrA196197macie:sideChainTyr196 donates a proton to C-alpha of the enolate intermediate to form the saturated ketone product. It is also thought to be able to stabilise the transition state state for the transfer of hydride by interacting with C-alpha.

Literature References

Notes:
Brown BJ
On the active site of Old Yellow Enzyme. Role of histidine 191 and asparagine 194.
J Biol Chem 1998 273 32753-32762
PubMed: 9830019
Brown BJ
The role of glutamine 114 in old yellow enzyme.
J Biol Chem 2002 277 2138-2145
PubMed: 11668181
Fox KM
Old yellow enzyme at 2 A resolution: overall structure, ligand binding, and comparison with related flavoproteins.
Structure 1994 2 1089-1105
PubMed: 7881908
Xu D
The role of threonine 37 in flavin reactivity of the old yellow enzyme.
Proc Natl Acad Sci U S A 1999 96 3556-3561
PubMed: 10097075
Kohli RM
The oxidative half-reaction of Old Yellow Enzyme. The role of tyrosine 196.
J Biol Chem 1998 273 32763-32770
PubMed: 9830020
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