RV2985 DIADENOSINE POLYPHOSPHATASE FROM M. TUBERCULOSIS, AN “INVASION” ENZYME HOMOLOG AND POTENTIAL NOVEL ANTIBIOTIC TARGET

Abstract

The Nudix hydrolases are a family of enzymes that cleave substrates containing a nucleoside diphosphate linked to some moiety, x, and are identified by the common signature sequence: GX5E7REUXEEXGU, where U= I, L, or V. We have been systematically discovering and characterizing Nudix hydrolases from M. tuberculosis to identify potential novel antibiotic targets. One such enzyme, Rv2985 diadenosine polyphosphatase, is a homolog to enzymes shown to be responsible for the invasiveness of pathogenic bacteria. We are purifying and characterizing Rv2985 as a possible candidate for the M. tuberculosis “invasion” enzyme. 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.