spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 2acu

E.C. namealdehyde reductase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 1.1.1.21
CSA Homologues of 2acu
CSA Entries With UniProtID P15121
CSA Entries With EC Number 1.1.1.21
PDBe Entry 2acu
PDBSum Entry 2acu
MACiE Entry 2acu

Literature Report

IntroductionHuman Aldehyde Reductase, sourced from Homo sapiens is a member of the aldo-keto reductase superfamily. It catalyses the NADPH-dependent reduction of a wide range of carbonyl compounds such as sugars, aldehyde metabolites, corticosteroid hormones and xenobiotic aldehydes. Interest in this enzyme stems from it's ability to reduce glucose and galactose, causing diabetic and galactosemic complications affecting the lens, retina, nerves and kidneys.
Mechansim1. The pro-R hydrogen of NADPH is transferred to the re face of the carbonyl group of the substrate. 2. The forming alcohol group is protonated by Tyr 48, which acts as a general acid. The Tyr 48 anion is stabilised electrostatically by Lys 77. Lys 77 is stabilised by Asp 43.
Reaction

Catalytic Sites for 2acu

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA4849macie:sideChainThe forming alcohol group is protonated by Tyr 48, which acts as a general acid.
AspA4344macie:sideChainAsp 43 electrostatically stabilises Lys 77.
LysA7778macie:sideChainLys 77 stabilises the Tyr 48 anion.

Literature References

Notes:
Bohren KM
Tyrosine-48 is the proton donor and histidine-110 directs substrate stereochemical selectivity in the reduction reaction of human aldose reductase: enzyme kinetics and crystal structure of the Y48H mutant enzyme.
Biochemistry 1994 33 2021-2032
PubMed: 8117659
spacer
spacer