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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1ebf

E.C. namehomoserine dehydrogenase
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz)
CSA Homologues of 1ebfThere are 12 Homologs
CSA Entries With UniProtID P31116
CSA Entries With EC Number
PDBe Entry 1ebf
PDBSum Entry 1ebf
MACiE Entry 1ebf

Literature Report

IntroductionHomo serine dehydrogenase belongs to the oxioreductase class of enzymes, although the residues implicated in catalysis are quite different from other enzymes within the class. It is involved in the NAD(P)H dependent reduction of L aspartate semi-aldehyde to L homoserine, a pathway not found within the animal kingdom. The enzyme has therefore been targeted for the development of antimycotic drugs.
MechansimThe NAD(P)H dependent reduction of L aspartate semi-aldehyde proceeds via hydride transfer. The hydride donating NAD(P)H cofactor is bound in the Rossmann fold, where enzyme-cofactor hydrogen bond interactions exist between cofactor phosphate moieties and sugar hydroxyl groups and the enzyme amide back bone groups. The amino substrate is thought to bind predominantly in the aldehyde rather than the hydrate form through hydrogen bond interactions with Asp 214, Glu 208, and a water molecule (460). The catalytic Lys 223 donates a proton to the developing alkoxide tetrahedral intermediate during hydride transfer. Asp 219 is key in positioning the catalytic residue, while the N terminal helix alpha J is important in stabilising the developing negative charge on the substrate carbonyl.

Catalytic Sites for 1ebf

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA223223macie:sideChainThe residue acts as the proton donor towards the developing anion on the substrate during hydride transfer from the NAD(P)H cofactor. Its position within the active site is dictated by hydrogen bonding to Asp 219.
AspA219219macie:sideChainhe residue is involved in orientating the catalytic Lys 223 towards the substrate by hydrogen bonding.

Literature References

DeLaBarre B
Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.
Nat Struct Biol 2000 7 238-244
PubMed: 10700284