Structural highlights
Function
MAZG_MYCTU Required to maintain the full capacity of the mycobacterium to respond to oxidative stress via the degradation of oxidation-induced damaged nucleotides. Hydrolyzes all canonical (d)NTPs, as well as mutagenic dUTP and 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). Also involved in the transcriptional activation of RelA in response to oxidative stress.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu LD, Sun Q, Fan XY, Zhong Y, Yao YF, Zhao GP. Mycobacterial MazG is a novel NTP pyrophosphohydrolase involved in oxidative stress response. J Biol Chem. 2010 Sep 3;285(36):28076-85. PMID:20529853 doi:10.1074/jbc.M109.088872
- ↑ 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. 2023 Mar 1;14:1137279. PMID:36937295 doi:10.3389/fmicb.2023.1137279
