 |
PDBsum entry 6ajs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
DNA binding protein
|
PDB id
|
|
|
|
6ajs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Covalent binding of uracil DNA glycosylase udgx to abasic DNA upon uracil excision.
|
|
|
Authors
|
|
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.
|
|
|
Ref.
|
|
Nat Chem Biol, 2019,
15,
607-614.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
