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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1evy
Original Entry
Title:
Oxidoreductase
Compound:
Glycerol-3-phosphate dehydrogenase
Mutant:
No
UniProt/Swiss-Prot:
P90551-P90551
EC Class:
1.1.1.8
Other CSA Entries:
Overview of all sites for 1evy
Homologues of 1evy
Entries for UniProt/Swiss-Prot: P90551
Entries for EC: 1.1.1.8
Other Databases:
PDB entry: 1evy
PDBsum entry: 1evy
UniProt/Swiss-Prot: P90551
IntEnz entry: 1.1.1.8
Literature Report:
Introduction:
Glycerol-3-phosphate dehydrogenase catalyses the interconversion of glycerol-3-phosphate (G3P) and Dihydroxyacetone-3-phosphate (DHAP), which is vital in the mitochondrial NAD/NADH shuttle. The dehydrogenase isolated from Leishmania mexicana (TRYPANOSOME) displays little sequence homology with the human system, thus may be a target for drug design.
Mechanism:
Lys 210 acts as the general base for the extraction of a proton from G3P, forming an intermediate with negative charge on the oxygen, stabilised by contacts with Thr 267. This intermediate then collapses via hydride transfer to the NAD+ cofactor to form the DHAP product.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 210 210Sidechain
Acid/baseSubstrate
Acts as a general base to extract a proton from G3P to form the charged intermediate thus facilitating hydride transfer from the substrate to NAD+
Evidence from paper Evidence concerns Evidence type
PubMed ID 12758080 Current protein Mutagenesis of residue
PubMed ID 12758080 Current protein Structural similarity to homologue of known mechanism
PubMed ID 12758080 Current protein Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
THRA 267 267Sidechain
ElectrostaticTransition state
Makes favourable contacts with the negatively charged oxygen of the intermediate to stabilise the transition state.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10801498 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 12758080 Current protein Conservation of residue
PubMed ID 12758080 Current protein Structural similarity to homologue of known mechanism
Notes:
Lys 125 and Asp 263 presumed to be involved only in binding substrate.
References:
1
Leishmania mexicana glycerol-3-phosphate dehydrogenase showed conformational changes upon binding a bi-substrate adduct.
J. Choe and D. Guerra and P. A. Michels and W. G. Hol
J Mol Biol 329, (2) 335-49, (2003).
12758080
2
A potential target enzyme for trypanocidal drugs revealed by the crystal structure of NAD-dependent glycerol-3-phosphate dehydrogenase from Leishmania mexicana.
S. Suresh and S. Turley and F. R. Opperdoes and P. A. Michels and W. G. Hol
Structure Fold Des 8, (5) 541-52, (2000).
10801498
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