1LLB

Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With ATMO-penicillin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.178 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Using steric hindrance to design new inhibitors of class C beta-lactamases.

Trehan, I.Morandi, F.Blaszczak, L.C.Shoichet, B.K.

(2002) Chem Biol 9: 971-980

  • DOI: https://doi.org/10.1016/s1074-5521(02)00211-9
  • Primary Citation of Related Structures:  
    1LL9, 1LLB

  • PubMed Abstract: 

    beta-lactamases confer resistance to beta-lactam antibiotics such as penicillins and cephalosporins. However, beta-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of beta-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R(1) side chain of beta-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective beta-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.


  • Organizational Affiliation

    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 303 E Chicago Avenue, Chicago, IL 60611, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
beta-lactamase
A, B
358Escherichia coliMutation(s): 0 
Gene Names: ampC
EC: 3.5.2.6
UniProt
Find proteins for P00811 (Escherichia coli (strain K12))
Explore P00811 
Go to UniProtKB:  P00811
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00811
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PCN
Query on PCN

Download Ideal Coordinates CCD File 
C [auth B]2-{1-[2-(2-AMINO-THIAZOL-4-YL)-2-METHOXYIMINO-ACETYLAMINO]-2-OXO-ETHYL}-5,5-DIMETHYL-THIAZOLIDINE-4-CARBOXYLIC ACID
C14 H19 N5 O5 S2
YVNKGXXVZIQNIV-RKMXGKDGSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PCN PDBBind:  1LLB IC50: 900 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.178 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.663α = 90
b = 76.734β = 116.186
c = 98.169γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-10-02
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description