Target intelligence / Profile preview

Very short patch repair endonuclease (Vsr)

Target
Vsr
Molecular classification
Enzyme, Endonuclease, DNA repair protein
01

Overview

The Very short patch repair endonuclease (Vsr) is a specialized bacterial enzyme that plays a pivotal role in the Very Short Patch (VSP) repair pathway. Its primary biological function is to correct T:G mismatches that arise from the spontaneous hydrolytic deamination of 5-methylcytosine to thymine, a common occurrence at DNA cytosine methyltransferase (Dcm) recognition sites, typically 5'-CCWGG-3' (PMID: 22912483, 10612397). Vsr recognizes these mismatches and introduces a strand-specific nick 5' to the mismatched thymine, which then allows DNA polymerase I and DNA ligase to restore the original C:G base pair (PMID: 11557809). This mechanism is essential for maintaining genomic stability and preventing C-to-T transition mutations in various bacteria, including Escherichia coli and Neisseria gonorrhoeae (PMID: 30161155). While Vsr is not currently a target for clinical therapeutics, it is a subject of significant interest in the study of bacterial mutation rates, evolution, and the development of antibiotic resistance (PMID: 25877151). Structurally, Vsr belongs to a unique class of endonucleases that share a fold with type II restriction enzymes but utilize a distinct catalytic mechanism involving a critical histidine residue and metal-ion coordination (PMID: 10612397).

Other names
Vsr endonucleaseVsr mismatch endonucleaseVery short patch repair proteinV.EcoKDcm
02

Mechanism of action

The enzyme recognizes T:G mismatches within specific DNA sequences (typically 5'-CCWGG-3') and catalyzes a strand-specific nick 5' to the mismatched thymine to initiate repair.

03

Biological functions

DNA repairVery short patch repairMismatch repairGenomic stability maintenance
04

Disease associations

InfectionAntibiotic resistance
05

Safety considerations

Therapeutic challenges include achieving high specificity for bacterial enzymes to avoid interfering with human DNA repair pathwaysPotential for bacterial compensation through alternative mismatch repair systems

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