7YH5

MazG(Mycobacterium tuberculosis)

Summary for 7YH5

• Entry DOI: 10.2210/pdb7yh5/pdb
• Descriptor: Nucleoside triphosphate pyrophosphohydrolase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: mazg, dutp, nucleoside triphosphate pyrophosphohydrolase, hydrolase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 6
• Total formula weight: 121903.71

Authors

Li, J.,Wang, S. (deposition date: 2022-07-12, release date: 2023-07-19, Last modification date: 2024-05-29)

Primary citation

Wang, S.,Gao, B.,Chen, A.,Zhang, Z.,Wang, S.,Lv, L.,Zhao, G.,Li, J.
Structural analysis of the housecleaning nucleoside triphosphate pyrophosphohydrolase MazG from Mycobacterium tuberculosis.
Front Microbiol, 14:1137279-1137279, 2023

PubMed Abstract: The housecleaning enzyme of (Mtb), MazG, is a nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) and can hydrolyze all canonical or non-canonical NTPs into NMPs and pyrophosphate. The 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 Å resolution, composed of two similar folded spherical domains in tandem. Unlike other all-α NTP pyrophosphatases, Mtb-MazG has an N-terminal extra region composed of three α-helices and five β-strands. The second domain is global, with five α-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 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 are indispensable for the catalytic activity of Mtb-MazG. Thus, our work provides new insights into understanding the molecular basis of MtbMazG.

PubMed: 36937295
DOI: 10.3389/fmicb.2023.1137279

Experimental method

X-RAY DIFFRACTION (2.7 Å)