6CT5

PptT PAP(CoA) 8918 complex

6CT5 の概要

• エントリーDOI: 10.2210/pdb6ct5/pdb
• 分子名称: 4'-phosphopantetheinyl transferase, COENZYME A, N-(2,6-diethylphenyl)-N'-(N-ethylcarbamimidoyl)urea, ... (7 entities in total)
• 機能のキーワード: inhibitor, complex, structural genomics, tb structural genomics consortium, tbsgc, transferase, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56976.57

構造登録者

Mosior, J.,Sacchettini, J.,TB Structural Genomics Consortium (TBSGC) (登録日: 2018-03-22, 公開日: 2019-02-06, 最終更新日: 2023-10-04)

主引用文献

Ballinger, E.,Mosior, J.,Hartman, T.,Burns-Huang, K.,Gold, B.,Morris, R.,Goullieux, L.,Blanc, I.,Vaubourgeix, J.,Lagrange, S.,Fraisse, L.,Sans, S.,Couturier, C.,Bacque, E.,Rhee, K.,Scarry, S.M.,Aube, J.,Yang, G.,Ouerfelli, O.,Schnappinger, D.,Ioerger, T.R.,Engelhart, C.A.,McConnell, J.A.,McAulay, K.,Fay, A.,Roubert, C.,Sacchettini, J.,Nathan, C.
Opposing reactions in coenzyme A metabolism sensitizeMycobacterium tuberculosisto enzyme inhibition.
Science, 363:-, 2019

PubMed Abstract: (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb's cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4'-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction. Thus, loss-of-function mutants of PptH displayed antimicrobial resistance. Our PptT-inhibitor cocrystal structure may aid further development of antimycobacterial agents against this long-sought target. The opposing reactions of PptT and PptH uncover a regulatory pathway in CoA physiology.

PubMed: 30705156
DOI: 10.1126/science.aau8959

実験手法

X-RAY DIFFRACTION (1.75934602056 Å)