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Publication Abstract from PubMed

The housecleaning enzyme of Mycobacterium tuberculosis (Mtb), MazG, is a nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) and can hydrolyze all canonical or non-canonical NTPs into NMPs and pyrophosphate. The Mycobacterium tuberculosis MazG (Mtb-MazG) contributes to antibiotic resistance in response to oxidative or nitrosative stress under dormancy, making it a promising target for treating TB in latent infection patients. However, the structural basis of Mtb-MazG is not clear. Here we describe the crystal structure of Mtb-MazG (1-185) at 2.7 A resolution, composed of two similar folded spherical domains in tandem. Unlike other all-alpha NTP pyrophosphatases, Mtb-MazG has an N-terminal extra region composed of three alpha-helices and five beta-strands. The second domain is global, with five alpha-helices located in the N-terminal domain. Gel-filtration assay and SAXS analysis show that Mtb-MazG forms an enzyme-active dimer in solution. In addition, the metal ion Mg(2+) is bound with four negative-charged residues Glu119, Glu122, Glu138, and Asp141. Different truncations and site-directed mutagenesis revealed that the full-length dimeric form and the metal ion Mg(2+) are indispensable for the catalytic activity of Mtb-MazG. Thus, our work provides new insights into understanding the molecular basis of Mtb-MazG.

Structural analysis of the housecleaning nucleoside triphosphate pyrophosphohydrolase MazG from Mycobacterium tuberculosis.,Wang S, Gao B, Chen A, Zhang Z, Wang S, Lv L, Zhao G, Li J Front Microbiol. 2023 Mar 1;14:1137279. doi: 10.3389/fmicb.2023.1137279. , eCollection 2023. PMID:36937295^[1]

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