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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1uqt

E.C. namealpha,alpha-trehalose-phosphate synthase (UDP-forming)
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 2.4.1.15
CSA Homologues of 1uqt1gz5,1uqu,
CSA Entries With UniProtID P31677
CSA Entries With EC Number 2.4.1.15
PDBe Entry 1uqt
PDBSum Entry 1uqt
MACiE Entry 1uqt

Literature Report

IntroductionE.coli Trehalose-6-phosphate synthase is part of the glycosyl transferase family 20, the retaining glycosyl transferases. It is able to catalyse the condensation between Glucose-6-phosphate and UDP-glucose to form trehalose-6-phosphate, an important metabolite for many bacteria and plants. Interest in the enzyme stems both from the study of the unusual reaction mechanism and the fact that it plays a key role in bacterial cell wall synthesis in M.tuberculosis, so is a possible target for antibiotics. It displays sequence and structural identity with the glycogen phosphorylases in particular, suggesting a common mechanism and evolutionary origin.
MechansimThe reaction mechanism has not been definitively characterised, but is most likely to proceed via an SNi like mechanism with the ring oxygen of the UDP glucose donating electron density to C1 to allow the UDP to leave the molecule. This forms an oxonium ion transition state stabilised by His 154 and Asp 361. Concerted attack from the nucleophilic OH group on the anomeric carbon of Glucose-6-phosphate ensures that the configuration is retained to give the disaccharide product. The activation of the OH towards nucleophilic attack is accomplished by the UDP moiety acting as a general base to remove a proton.
Reaction

Catalytic Sites for 1uqt

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA361362macie:sideChainThe oxonium ion's different structure relative to the substrate pushes its 3C OH group into alignment with the side chain carbonyl of Asp 361, thus allowing a hydrogen bond to form stabilising the transition state for the reaction.
HisA154155macie:mainChainCarbonylCarbonyl oxygen lone pair contributes electron density to the positively charged ring oxygen to stabilise the oxonium ion transition state that forms as Glucose-6-phosphate attacks UDP glucose.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB361362macie:sideChainThe oxonium ion's different structure relative to the substrate pushes its 3C OH group into alignment with the side chain carbonyl of Asp 361, thus allowing a hydrogen bond to form stabilising the transition state for the reaction.
HisB154155macie:mainChainCarbonylCarbonyl oxygen lone pair contributes electron density to the positively charged ring oxygen to stabilise the oxonium ion transition state that forms as Glucose-6-phosphate attacks UDP glucose.

Literature References

Notes:
Gibson RP
Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA.
Chem Biol 2002 9 1337-1346
PubMed: 12498887
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