Summary information and primary citation
- PDB-id
- 4yph; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- hydrolase-DNA
- Method
- X-ray (2.32 Å)
- Summary
- Crystal structure of muty bound to its anti-substrate with the disulfide cross-linker reduced
- Reference
- Wang L, Lee SJ, Verdine GL (2015): "Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase." J.Biol.Chem., 290, 17096-17105. doi: 10.1074/jbc.M115.657866.
- Abstract
- The highly mutagenic A:oxoG 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 hMYH 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.
