Overview for MACiE Entry M0071
EC Number: 126.96.36.199 (A member of the Hydrolases, Glycosylases, Hydrolysing N-glycosyl compounds)
Enzyme Name: uridine nucleosidase
Biological Species: Escherichia coli (Bacteria)
Catalytic Chain UniprotKB Accession Codes:
- P12295 - Uracil-DNA glycosylase
Representative PDB Code: 1eug - CRYSTAL STRUCTURE OF ESCHERICHIA COLI URACIL DNA GLYCOSYLASE AND ITSCOMPLEXES WITH URACIL AND GLYCEROL: STRUCTURE AND GLYCOSYLASEMECHANISM REVISITED (Resolution = 1.60 Å).
Catalytic CATH Codes:
Display structure information
It is unknown whether this reaction is reversible or not.
Overall Comment: Classically an acid/base mechanism has been employed but, new evidence suggests an alternative mechanism where the glycosylic bond is cleaved in a dissociative nucleophilic substitution reaction, brought about by the control of substrate conformation energy and stereoelectronic effects within the active site.
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Stepwise Description of the Reaction
|Step 1||The structural constraints imposed upon the uridine deoxyribose ring by Tyr 66 and Phe 77 induce unimolecular elimination to form a transient oxonium species and an anionic precursor of uracil|
|Step 2||The transient oxonium species is attacked by water, forming the 1-alpha hydroxy group of the D-ribose product. The anionic intermediate is stabilised though hydrogen bonding to His187, and is then protonated from the attacking water. |
|Step 3||The intermediate tautomerises to form the uracil product. |
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Catalytic Residues Involved
||Location of Function
- G. Xiao et al. (1999), Proteins, 35, 13-24. Crystal structure of Escherichia coli uracil DNA glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited.
- S. S. Parikh et al. (2000), Proc. Natl Acad. Sci. USA, 97, 5083-5088. Uracil-DNA glycosylase-DNA substrate and product structures: conformational strain promotes catalytic efficiency by coupled stereoelectronic effects.
- S. S. Parikh et al. (2000), Mutation Research, 460, 183-199. Lessons learned from structural results on uracil-DNA glycosylase.
Homologue information for M0071 (1eug)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
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