6kgu | pdb_00006kgu

Crystal structure of Penicillin binding protein 3 (PBP3) from Mycobacterium tuerculosis, complexed with aztreonam

spinqualitylabelsall models 6kgu, resolution 2.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kgu is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.106Å Ligands: AZR, CO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PBPB_MYCTU Synthesis of cross-linked peptidoglycan from the lipid intermediates. Publication Abstract from PubMed Because of beta-lactamase-mediated resistance, beta-lactam antibiotics were long considered ineffective drugs for tuberculosis (TB) treatment. However, some beta-lactams, including meropenem and faropenem, are being re-evaluated in patients infected with TB. Penicillin-binding protein (PBP) 3, or ftsI, is an essential transpeptidase in Mycobacterium tuberculosis (Mtb) required for cell division, and thus it is an important drug target. Structures of apo MtbPBP3 and of complexes with five beta-lactams, including meropenem and faropenem, reveal how they cause inactivation via formation of hydrolytically stable acyl-enzyme complexes. The structures reveal unique features of the antibiotic interactions, both in terms of differences in their binding to MtbPBP3 and in comparison with structures of other PBPs and serine beta-lactamases, including the tautomerization status of the carbapenem-derived acyl-enzyme complexes. The results suggest that rather than hoping PBP inhibitors developed for other infections will work against TB, work should focus on developing PBP inhibitors specialized for treating TB. SIGNIFICANCE STATEMENT: The structures of Mycobacterium tuberculosis penicillin-binding protein 3, an essential protein in M. tuberculosis, in complex with a number of widely used beta-lactam antibiotics (e.g., meropenem, aztreonam, and amoxicillin) were solved. These data provide new insights for next-generation rational approaches to design tuberculosis (TB)-specific beta-lactam or nonlactam antibiotics. This manuscript is a seminal article in the field of anti-TB drug discovery and suitable for the broad readership. Structures of Mycobacterium tuberculosis Penicillin-Binding Protein 3 in Complex with Five beta-Lactam Antibiotics Reveal Mechanism of Inactivation.,Lu Z, Wang H, Zhang A, Liu X, Zhou W, Yang C, Guddat L, Yang H, Schofield CJ, Rao Z Mol Pharmacol. 2020 Apr;97(4):287-294. doi: 10.1124/mol.119.118042. Epub 2020 Feb, 21. PMID:32086254 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Penicillin-binding protein 3D structures

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