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Catalytic Site Atlas

CSA LITERATURE entry for 1qlh

E.C. namealcohol dehydrogenase
SpeciesEquus caballus (Horse)
E.C. Number (IntEnz)
CSA Homologues of 1qlhThere are 114 Homologs
CSA Entries With UniProtID P00327
CSA Entries With EC Number
PDBe Entry 1qlh
PDBSum Entry 1qlh
MACiE Entry M0256

Literature Report

IntroductionAlcohol dehydrogenase is the enzyme responsible for the conversion of alcohol to acetaldehyde that occurs in the cytoplasm, one of the three routes whereby acetaldehyde can be formed from alcohol before it passes into the mitochondria for the completion of the breakdown process. As a result the enzyme plays a vital role in alcohol metabolism, and inability to process alcohol is most commonly caused by deficiency. The enzyme relies on NAD+ as a cofactor for the reaction, and belongs to the zinc containing dehydrogenase family, class I subfamily.
MechansimThe enzyme is able to oxidise alcohol using concomitant reduction of NAD+. The substrate binds to a zinc ion at the active site, which allows deprotonation of the OH group by Ser 48 and His 51 in a proton relay system, because the zinc ion stabilises the oxyanion thus reducing the pKa of the OH to around 8.4. This allows hydride transfer from C2 to the NAD+ with the oxygen lone pair overlapping with the sigma* orbital of C2 to create the double bond that characterises the product.

Catalytic Sites for 1qlh

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA4849macie:sideChainActs as a general base to deprotonate the OH group of the alcohol substrate.
HisA5152macie:sideChainReduces the pKa of Ser 48 by accepting a proton from it to allow it to act as a general base

Literature References

Eklund H
Binding of substrate in a ternary complex of horse liver alcohol dehydrogenase.
J Biol Chem 1982 257 14349-14358
PubMed: 6754727
Ramaswamy S
Substitutions in a flexible loop of horse liver alcohol dehydrogenase hinder the conformational change and unmask hydrogen transfer.
Biochemistry 1999 38 13951-13959
PubMed: 10529241