E. coli PBP1b in complex with acyl-ampicillin and moenomycin

Experimental Data Snapshot

  • Resolution: 2.70 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.241 

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This is version 1.3 of the entry. See complete history


Structural Insights into Inhibition of Escherichia coli Penicillin-binding Protein 1B.

King, D.T.Wasney, G.A.Nosella, M.Fong, A.Strynadka, N.C.

(2017) J Biol Chem 292: 979-993

  • DOI: https://doi.org/10.1074/jbc.M116.718403
  • Primary Citation of Related Structures:  
    5HL9, 5HLA, 5HLB, 5HLD

  • 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.

  • Organizational Affiliation

    From the Department of Biochemistry and Molecular Biology and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Penicillin-binding protein 1B747Escherichia coli K-12Mutation(s): 0 
Gene Names: mrcBpbpFponBb0149JW0145
EC: (PDB Primary Data), 3.4 (PDB Primary Data)
Membrane Entity: Yes 
Find proteins for P02919 (Escherichia coli (strain K12))
Explore P02919 
Go to UniProtKB:  P02919
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02919
Sequence Annotations
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Query on M0E

Download Ideal Coordinates CCD File 
C69 H106 N5 O34 P
Query on AIX

Download Ideal Coordinates CCD File 
B [auth A](2R,4S)-2-[(1R)-1-{[(2R)-2-amino-2-phenylacetyl]amino}-2-oxoethyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
C16 H21 N3 O4 S
Experimental Data & Validation

Experimental Data

  • Resolution: 2.70 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.241 
  • Space Group: P 2 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.44α = 90
b = 63.8β = 90
c = 299.35γ = 90
Software Package:
Software NamePurpose
xia2data reduction
Aimlessdata scaling

Structure Validation

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Ligand Structure Quality Assessment 

Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
Canadian Institutes of Health Research (CIHR)Canada--
Howard Hughes Medical Institute (HHMI)United States--
Canadian Foundation for InnovationCanada--
British Columbia Knowledge Development FundCanada--
Canada Research Chair ProgramsCanada--

Revision History  (Full details and data files)

  • Version 1.0: 2016-12-14
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence
  • Version 1.2: 2019-05-08
    Changes: Data collection, Database references
  • Version 1.3: 2019-11-20
    Changes: Author supporting evidence