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Rv2985 diadenosine polyphosphatase from M. tuberculosis, an “invasion” enzyme homolog and potential novel antibiotic target
Author(s) -
Ramos Julian,
Thomson Joshua,
Sheibley Daniel,
Glick Sarah,
O’Handley Suzanne F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1001-a
Subject(s) - cleave , enzyme , biochemistry , nucleoside , cofactor , chemistry , pathogen , antibiotics , biology , microbiology and biotechnology
The Nudix hydrolases are enzymes that cleave nucleoside diphosphates linked to some moiety, x, and are identified by the common signature sequence: GX5E7REUXEEXGU (U= I, L, or V). We are systematically discovering and characterizing Nudix hydrolases from M. tuberculosis. Rv2985 diadenosine polyphosphatase is a TB homolog to diadenosine polyphosphatases shown to be responsible for the invasiveness of pathogenic bacteria. Rv2985 cleaves Ap4A, Ap5A and Ap6A with nearly comparable activity. Characteristic of Nudix hydrolases, a divalent metal cofactor is required, and Rv2985 has an alkaline pH optimum (pH 8.5). Regardless of which diadenosine polyphosphate is cleaved, ATP is always a resulting product, and it is always the fourth phosphorus from one of the adenosines which is attacked during hydrolysis. Recently we have subcloned and purified a His‐tagged protein, and showed that it retains full expression, solubility, and activity, as compared to wild type, and purifies by affinity chromatography as one pure band. Blocking the ability of a pathogen such as M. tuberculosis to be able to invade its human host may be an excellent target for the development of new antibiotics. Supported by an NIH AREA grant.