6ct5 | pdb_00006ct5

PptT PAP(CoA) 8918 complex

spinqualitylabelsall models 6ct5, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ct5 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: COA, DMS, FD7, GOL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mycobacterium tuberculosis (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. Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition.,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 SM, Aube J, Yang G, Ouerfelli O, Schnappinger D, Ioerger TR, Engelhart CA, McConnell JA, McAulay K, Fay A, Roubert C, Sacchettini J, Nathan C Science. 2019 Feb 1;363(6426). pii: 363/6426/eaau8959. doi:, 10.1126/science.aau8959. PMID:30705156 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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