5HLB: E. Coli Pbp1b In Complex With Acyl-aztreonam And Moenomycin

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 beta-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 beta-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.
PDB ID: 5HLBDownload
MMDB ID: 145596
PDB Deposition Date: 2016/1/14
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 2.42  Å
Source Organism:
Similar Structures:
Biological Unit for 5HLB: dimeric; determined by author and by software (PISA)
Molecular Components in 5HLB
Label Count Molecule
Proteins (2 molecules)
Penicillin-binding Protein 1B(Gene symbol: mrcB)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB