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Catalytic Site Atlas

CSA LITERATURE entry for 1eq2

E.C. nameADP-glyceromanno-heptose 6-epimerase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz)
CSA Homologues of 1eq2There are 273 Homologs
CSA Entries With UniProtID P67910
CSA Entries With EC Number
PDBe Entry 1eq2
PDBSum Entry 1eq2
MACiE Entry 1eq2

Literature Report

IntroductionADP -L-glycero-D-mannoheptose 6-epimerase (AGME) is classified as a member of the short-chain dehydrogenase/reductase (SDR) superfamily, on the grounds of its high structural similarity with UDP-galactose epimerase and its positioning of conserved catalytic residues. AGME catalyses the interconversion between ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose, the last step in the biosynthesis of the precursor of L-glycero-D-mannoheptose. The enzyme is an NADP dependent epimerase which shows a diminished activity with NAD.
MechansimThe enzyme bound NAD+ coenzyme accepts a hydride from the substrate's C-6. Hydride transfer is promoted by deprotonation at C6-OH. The resulting keto intermediate flips in the active site to allow return of the hydride from NADH to the other face of the substrate, forming the alternative epimer. The enzyme is able to catalyse both the forward and reverse reactions, with separate catalytic residues acting as the base in each direction.

Catalytic Sites for 1eq2

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA116116macie:sideChainThe residue acts as a proton shuttle between the sugar substrate and the phenolic side chain of Tyr 140.
TyrA140140macie:sideChainThe residue acts as a general base towards the C6-OH hydrogen of ADP-D-glycero-D-mannoheptose, facilitating the removal of hydride to the NAD cofactor via a proton shuttle with Ser 116.
LysA178178macie:sideChainhe residue acts as a general base towards the ADP-L-glycero-D-mannoheptose substrate in the reverse reaction, removing the C6-OH proton, facilitating hydride transfer to NAD+ cofactor.

Literature References

Notes:Only in the most recent paper listed (2007) does any information for the role of Lys 178 emerge. The two base mechanism the paper proposes goes against the mechanism of the structurally related UDP galactose, although the papers looking at this related structural homologue do correctly implicate a proton relay between the catalytic Ser and Tyr residues. I have included these papers as references for the residues involved in the proton relay even though the overall mechanism has been superseded.
Thoden JB
High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol.
Protein Sci 1996 5 2149-2161
PubMed: 8931134
Deacon AM
The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist.
Structure 2000 8 453-462
PubMed: 10896473
Morrison JP
A two-base mechanism for Escherichia coli ADP-L-glycero-D-manno-heptose 6-epimerase.
Biochemistry 2007 46 3916-3924
PubMed: 17316025