5HLD
E. coli PBP1b in complex with acyl-CENTA and moenomycin
Summary for 5HLD
| Entry DOI | 10.2210/pdb5hld/pdb |
| Related | 5HL9 5HLA 5HLB |
| Descriptor | Penicillin-binding protein 1B, (2S)-5-methylidene-2-{(1R)-2-oxo-1-[(thiophen-2-ylacetyl)amino]ethyl}-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid, MOENOMYCIN, ... (4 entities in total) |
| Functional Keywords | penicillin-binding protein, inhibitor complex, transpeptidase, transglycosylase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 1 |
| Total formula weight | 85199.32 |
| Authors | King, D.T.,Strynadka, N.C.J. (deposition date: 2016-01-14, release date: 2016-12-14, Last modification date: 2024-11-20) |
| Primary citation | King, D.T.,Wasney, G.A.,Nosella, M.,Fong, A.,Strynadka, N.C. Escherichia coli Penicillin-Binding Protein 1B: Structural Insights into Inhibition. J. Biol. Chem., 2016 Cited by PubMed Abstract: In Escherichia coli, the peptidoglycan cell wall is synthesized by bifunctional penicillin-binding proteins such as PBP1b that have both transpeptidase and transglycosylase activities. The PBP1b transpeptidase domain is a major target of β-lactams, and therefore it is important to attain a detailed understanding of its inhibition. The peptidoglycan glycosyltransferase domain of PBP1b is also considered an excellent antibiotic target yet is not exploited by any clinically approved antibacterials. Herein, we adapt a pyrophosphate sensor assay to monitor PBP1b-catalyzed glycosyltransfer and present an improved crystallographic model for inhibition of the PBP1b glycosyltransferase domain by the potent substrate analog moenomycin. We elucidate the structure of a previously disordered region in the glycosyltransferase active site and discuss its implications with regards to peptidoglycan polymerization. Furthermore, we solve the crystal structures of E. coli PBP1b bound to multiple different β-lactams in the transpeptidase active site and complement these data with gel-based competition assays to provide a detailed structural understanding of its inhibition. Taken together, these biochemical and structural data allow us to propose new insights into inhibition of both enzymatic domains in PBP1b. PubMed: 27899450DOI: 10.1074/jbc.M116.718403 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.31 Å) |
Structure validation
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