 |
PDBsum entry 4ypr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/DNA
|
PDB id
|
|
|
|
4ypr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for avoidance of promutagenic DNA repair by muty adenine DNA glycosylase.
|
|
|
Authors
|
|
L.Wang,
S.J.Lee,
G.L.Verdine.
|
|
|
Ref.
|
|
J Biol Chem, 2015,
290,
17096-17105.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The highly mutagenic A:oxoG (8-oxoguanine) base pair in DNA most frequently
arises by aberrant replication of the primary oxidative lesion C:oxoG. This
lesion is particularly insidious because neither of its constituent nucleobases
faithfully transmit genetic information from the original C:G base pair. Repair
of A:oxoG is initiated by adenine DNA glycosylase, which catalyzes hydrolytic
cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY
in bacteria and MUTYH in humans, scrupulously avoid processing of C:oxoG because
cleavage of the C residue in C:oxoG would actually promote mutagenic conversion
to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY,
using a synthetic crystallography approach to capture the enzyme in the process
of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only
fleetingly. We find that MutY uses two distinct strategies to avoid presentation
of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves
as a decoy for C, and secondly, repulsive forces with a key active site residue
prevent stable insertion of C into the nucleobase recognition pocket within the
enzyme active site.
|
|
|
|
|
|
|
