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Overview for MACiE Entry M0071

Version history

General Information

EC Number: 3.2.2.3 (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

Overall Reaction:

Image of uridine

Image of water

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Image of uracil

Image of D-ribose

uridine
C00299
CHEBI:16704
water
C00001
CHEBI:15377
uracil
C00106
CHEBI:17568
D-ribose
C00121
CHEBI:16988

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 1The 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 2The 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 3The intermediate tautomerises to form the uracil product.

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Catalytic Residues Involved

Type Number Chain Location of Function
Phe 77 A Side Chain
Tyr 66 A Side Chain
His 187 A Side Chain

References

  1. 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.
    Medline: 10090282
  2. 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.
    Medline: 10805771
  3. S. S. Parikh et al. (2000), Mutation Research, 460, 183-199. Lessons learned from structural results on uracil-DNA glycosylase.
    Medline: 10946228

Homologue information for M0071 (1eug)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

GOA logo
uracil DNA N-glycosylase activity (molecular function)
DNA repair (biological process)
base-excision repair (biological process)
hydrolase activity, hydrolyzing N-glycosyl compounds (molecular function)
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