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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1do8

E.C. namemalate dehydrogenase (oxaloacetate-decarboxylating)
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 1.1.1.38
CSA Homologues of 1do8There are 18 Homologs
CSA Entries With UniProtID P23368
CSA Entries With EC Number 1.1.1.38
PDBe Entry 1do8
PDBSum Entry 1do8
MACiE Entry M0021

Literature Report

IntroductionMalic enzymes are found in most living organisms including bacteria and humans. They catalyse the conversion of L-malate to pyruvate with the concomitant reduction of the cofactor NAD+ or NADP+. In mammals three isoforms have been identified, a cytosolic NADP+ dependent enzyme, a mitochondrial NADP+ dependent enzyme and a a mitochondrial NAD+ dependent enzyme. Each has different roles for example the mitochondrial NAD+ dependent enzyme plays important roles in the metabolism of glutamine for energy production in rapidly proliferating tissues and tumours.
MechansimThe catalysis by malate enzymes generally proceeds in two steps - dehydrogenation of the malate to produce oxaloacetate and then decarboxylation to produce pyruvate. A bound metal divalent cation (Mg2+ or Mn2+) polarises the C2 hydroxyl of malate for dehydrogenation and stabilises the C2 enolic oxygen for decarboxylation. Lys183 is the most likely candidate for a general acid to protonate the enol-pyruvate product of decarboxylation. Tyr112 plays a vital role in the dehydrogenation reaction although the structural basis for such a role is yet to be determined. Many other residues are involved in substrate binding and stabilisation.
Reaction

Catalytic Sites for 1do8

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA278278macie:sideChain
LysA183183macie:sideChain
TyrA112112macie:sideChain

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysB1183183macie:sideChain
AspB1278278macie:sideChain
TyrB1112112macie:sideChain

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspC2278278macie:sideChain
LysC2183183macie:sideChain
TyrC2112112macie:sideChain

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspD3278278macie:sideChain
TyrD3112112macie:sideChain
LysD3183183macie:sideChain

Literature References

Notes:
Yang Z
Structure of a closed form of human malic enzyme and implications for catalytic mechanism.
Nat Struct Biol 2000 7 251-257
PubMed: 10700286
Tao X
Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism.
Structure 2003 11 1141-1150
PubMed: 12962632
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