4YPH: Crystal Structure Of Muty Bound To Its Anti-substrate With The Disulfide Cross-linker Reduced

Citation:
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.
PDB ID: 4YPHDownload
MMDB ID: 129626
PDB Deposition Date: 2015/3/13
Updated in MMDB: 2015/07
Experimental Method:
x-ray diffraction
Resolution: 2.32  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4YPH: trimeric; determined by author and by software (PISA)
Molecular Components in 4YPH
Label Count Molecule
Protein (1 molecule)
1
A/g-specific Adenine Glycosylase
Molecule annotation
Nucleotides(2 molecules)
1
DNA (5'-d(*ap*ap*gp*ap*cp*(8og)p*tp*gp*gp*ap*c)-3')
Molecule annotation
1
DNA (5'-d(tp*gp*tp*cp*cp*ap*cp*gp*tp*cp*t)-3')
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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