7bdw | pdb_00007bdw

Crystal structure of mycobacterial PptAb in complex with ACP and compound 8918

spinqualitylabelsall models 7bdw, resolution 2.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bdw is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.55Å Ligands: COA, FD7, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B1MD73_MYCA9 Publication Abstract from PubMed Owing to their role in activating enzymes essential for bacterial viability and pathogenicity, phosphopantetheinyl transferases represent novel and attractive drug targets. In this work, we examined the inhibitory effect of the aminido-urea 8918 compound against the phosphopantetheinyl transferases PptAb from Mycobacterium abscessus and PcpS from Pseudomonas aeruginosa, two pathogenic bacteria associated with cystic fibrosis and bronchiectasis, respectively. Compound 8918 exhibits inhibitory activity against PptAb but displays no activity against PcpS in vitro, while no antimicrobial activity against Mycobacterium abscessus or Pseudomonas aeruginosa could be detected. X-ray crystallographic analysis of 8918 bound to PptAb-CoA alone and in complex with an acyl carrier protein domain in addition to the crystal structure of PcpS in complex with CoA revealed the structural basis for the inhibition mechanism of PptAb by 8918 and its ineffectiveness against PcpS. Finally, in crystallo screening of potent inhibitors from the National Cancer Institute library identified a hydroxypyrimidinethione derivative that binds PptAb. Both compounds could serve as scaffolds for the future development of phosphopantetheinyl transferases inhibitors. Phosphopantetheinyl transferase binding and inhibition by amidino-urea and hydroxypyrimidinethione compounds.,Carivenc C, Maveyraud L, Blanger C, Ballereau S, Roy-Camille C, Nguyen MC, Genisson Y, Guilhot C, Chalut C, Pedelacq JD, Mourey L Sci Rep. 2021 Sep 10;11(1):18042. doi: 10.1038/s41598-021-97197-4. PMID:34508141 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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