PDBsum entry 6ajs

DNA binding protein

PDB id: 6ajs

Contents

Protein chain

207 a.a.

Ligands

SF4

Waters ×216

PDB id:

6ajs

Name:

DNA binding protein

Title:

H109s mutant form of uracil DNA glycosylase x.

Structure:

Uracil DNA glycosylase superfamily protein. Chain: a. Engineered: yes. Mutation: yes

Source:

Mycobacterium smegmatis mc2 155. Organism_taxid: 246196. Strain: mc2 155. Gene: msmeg_0265. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.63Å R-factor: 0.163 R-free: 0.197

Authors:

W.C.Ahn,S.Aroli,U.Varshney,E.J.Woo

Key ref:

W.C.Ahn et al. (2019). Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision. Nat Chem Biol, 15, 607-614. PubMed id: 31101917 DOI: 10.1038/s41589-019-0289-3

Date:

28-Aug-18 Release date: 29-May-19

Protein chain

A0QP43  (A0QP43_MYCS2) -  Type-4 uracil-DNA glycosylase from Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)

Seq: 209 a.a.

Struc: 207 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/s41589-019-0289-3

Nat Chem Biol 15:607-614 (2019)

PubMed id: 31101917

Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision.

W.C.Ahn, S.Aroli, J.H.Kim, J.H.Moon, G.S.Lee, M.H.Lee, P.B.Sang, B.H.Oh, U.Varshney, E.J.Woo.

ABSTRACT

Uracil DNA glycosylases (UDGs) are important DNA repair enzymes that excise uracil from DNA, yielding an abasic site. Recently, UdgX, an unconventional UDG with extremely tight binding to DNA containing uracil, was discovered. The structure of UdgX from Mycobacterium smegmatis in complex with DNA shows an overall similarity to that of family 4 UDGs except for a protruding loop at the entrance of the uracil-binding pocket. Surprisingly, H109 in the loop was found to make a covalent bond to the abasic site to form a stable intermediate, while the excised uracil remained in the pocket of the active site. H109 functions as a nucleophile to attack the oxocarbenium ion, substituting for the catalytic water molecule found in other UDGs. To our knowledge, this change from a catalytic water attack to a direct nucleophilic attack by the histidine residue is unprecedented. UdgX utilizes a unique mechanism of protecting cytotoxic abasic sites from exposure to the cellular environment.