9GMT

Mtb PNPase Rv2783c Mutant L328F

これはPDB形式変換不可エントリーです。

9GMT の概要

• エントリーDOI: 10.2210/pdb9gmt/pdb
• EMDBエントリー: 51455
• 分子名称: Polyribonucleotide nucleotidyltransferase, RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*AP*AP*AP*AP*AP*AP*AP*A)-3'), 1-[[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazol-4-yl]carbonylamino]phenyl]phenyl]carbonylamino]cyclopentane-1-carboxylic acid (3 entities in total)
• 機能のキーワード: pnpase, gpsi, rna degradosome, pnpase inhibitor, rna
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 196908.55

構造登録者

Griesser, T.,Sander, P. (登録日: 2024-08-29, 公開日: 2025-06-25, 最終更新日: 2025-07-09)

主引用文献

Griesser, T.,Wang, R.,Angona, I.P.,Rogenmoser, J.,Obrist, J.,Schneider, G.,Sander, P.
Selective inhibition of Mycobacterium tuberculosis GpsI unveils a novel strategy to target the RNA metabolism.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: Polyribonucleotide nucleotidyl-transferases (PNPases) play a critical role in the degradation of mRNA. The mycobacterial PNPase, guanosine penta-phosphate synthase I (GpsI), is an essential enzyme in Mycobacterium tuberculosis (Mtb), collaborating with endoribonucleases and helicases to process RNA. In this study, we identify GpsI as a novel and underexplored drug target. The inhibitor 1-(4'-(2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido)-[1,1'-biphenyl]-4-caroxamido) cyclopentane-1-carboxylic acid (X1), discovered through a whole-cell screening, specifically inhibits GpsI activity in biochemical assays. Biochemical and physiological analyses of engineered GpsI variants and recombinant Mycobacterium smegmatis pinpoint amino acids 328 and 527 as critical residues for the selective activity of X1 against Mtb complex. High-resolution cryo-electron microscopy analysis of the ternary GpsI-X1-poly(A) complex elucidates the drug-binding pocket, providing insight into its mechanism of action. This study introduces a potent inhibitor targeting the underexplored Mtb-GpsI and offers a molecular explanation for its selective specificity.

PubMed: 40530695
DOI: 10.1093/nar/gkaf529

実験手法

ELECTRON MICROSCOPY (1.93 Å)