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Publication Abstract from PubMed

A uracil DNA glycosylase (UDG) from Mycobacterium smegmatis (MsmUdgX) shares sequence similarity with family 4 UDGs and forms exceedingly stable complexes with single-stranded uracil-containing DNAs (ssDNA-Us) that are resistant to denaturants. However, MsmUdgX has been reported to be inactive in excising uracil from ssDNA-Us and the underlying structural basis is unclear. Here, we report high-resolution crystal structures of MsmUdgX in the free, uracil- and DNA-bound forms, respectively. The structural information, supported by mutational and biochemical analyses, indicates that the conserved residue His109 located on a characteristic loop forms an irreversible covalent linkage with the deoxyribose at the apyrimidinic site of ssDNA-U, thus rendering the enzyme unable to regenerate. By proposing the catalytic pathway and molecular mechanism for MsmUdgX, our studies provide an insight into family 4 UDGs and UDGs in general.

Suicide inactivation of the uracil DNA glycosylase UdgX by covalent complex formation.,Tu J, Chen R, Yang Y, Cao W, Xie W Nat Chem Biol. 2019 Jun;15(6):615-622. doi: 10.1038/s41589-019-0290-x. Epub 2019 , May 17. PMID:31101915^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.