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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1i8t

E.C. nameUDP-galactopyranose mutase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 5.4.99.9
CSA Homologues of 1i8t
CSA Entries With UniProtID P37747
CSA Entries With EC Number 5.4.99.9
PDBe Entry 1i8t
PDBSum Entry 1i8t
MACiE Entry 1i8t

Literature Report

IntroductionUridine diphosphogalactofuranose (UDP-Galf ) is the precursor of the D-galactofuranose (Galf) residues found in bacterial and parasitic cell walls, including those of many pathogens, such as Mycobacterium tuberculosis and Trypanosoma cruzi. The mutase enzyme is essential for the viability of mycobacteria and is not found in humans, making it a viable therapeutic target. A novel mechanism involving reduced FAD acting as a nucleophile has been proposed.
MechansimNucleophilic attack by N5 of reduced FAD on C1 of UDP-Galp via an SN1 or SN2 type mechanism results in the loss of UDP. The charged leaving group is stabilised by electrostatic and hydrogen bonding interactions with Arg170 and Arg278. The imminium intermediate is formed by a second attack of FAD N5 lone pair on C1 of the sugar. This results in the opening of the ring at the OH6 position. The negative charge at N1 is required to increase the nucleophilicity of N5.
The intramolecular nucleophilic attack by OH4 on the imminium group forms a new galactofuranose ring still bound to N5 of the reduced FAD. To release the sugar from the enzyme cofactor, UDP attacks the C1 position leading to lysis of the C1-N5 bond and release of UDP-Galf.
Reaction

Catalytic Sites for 1i8t

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA348348macie:sideChainCharge stabilisation.
ArgA278278macie:sideChainElectrostatic stabilisation of the UDP leaving group.
ArgA170170macie:sideChainElectrostatic stabilisation of the UDP leaving group.
GluA298298macie:sideChainCharge stabilisation.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB348348macie:sideChainCharge stabilisation.
ArgB278278macie:sideChainElectrostatic stabilisation of the UDP leaving group.
GluB298298macie:sideChainCharge stabilisation.
ArgB170170macie:sideChainElectrostatic stabilisation of the UDP leaving group.

Literature References

Notes:The specific role of Asp348 and Glu298 in the catalytic mechanism have yet to be specified accurately. Their presence is however essential to catalysis.
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