1BLC

INHIBITION OF BETA-LACTAMASE BY CLAVULANATE: TRAPPED INTERMEDIATES IN CRYOCRYSTALLOGRAPHIC STUDIES


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Inhibition of beta-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies.

Chen, C.C.Herzberg, O.

(1992) J Mol Biol 224: 1103-1113

  • DOI: https://doi.org/10.1016/0022-2836(92)90472-v
  • Primary Citation of Related Structures:  
    1BLC

  • PubMed Abstract: 

    Crystallographic studies of the complex between beta-lactamase and clavulanate reveal a structure of two acyl-enzymes with covalent bonds at the active site Ser70, representing two different stages of inhibitor degradation alternately occupying the active site. Models that are consistent with biochemical data are derived from the electron density map and refined at 2.2 A resolution: cis enamine, in which the carboxylate group of the clavulanate molecule makes a salt bridge with Lys234 of beta-lactamase; decarboxylated trans enamine, which is oriented away from Lys234. For both acyl-enzymes, the carbonyl oxygen atom of the ester group occupies the oxyanion hole in a manner similar to that found in inhibitor binding to serine proteases. Whereas the oxygen atom in the trans product is optimally positioned in the oxyanion hole, that of the cis product clashes with the main-chain nitrogen atom of Ser70 and the beta-carbon atom of the adjacent Ala69. In contrast to cis to trans isomerization in solution that relieves the steric strain inherent in a cis double bond, at the enzyme-inhibitor interface two additional factors play an important role. The salt bridge enhances the stability of the cis product, while the steric strain introduced by the short contacts with the protein reduces its stability.


  • Organizational Affiliation

    Center for Advanced Research in Biotechnology, Maryland Biotechnology Institute, University of Maryland, Rockville 20850.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-LACTAMASE257Staphylococcus aureusMutation(s): 0 
EC: 3.5.2.6
UniProt
Find proteins for P00807 (Staphylococcus aureus)
Explore P00807 
Go to UniProtKB:  P00807
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00807
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CEM
Query on CEM

Download Ideal Coordinates CCD File 
C [auth A]N-(1-CARBOXY-2-HYDROXY-4-OXO-BUTYL)-N-(3-OXO-CISPROPENYL)AMINE
C8 H11 N O5
DIQBZADGQQVQIO-WHFQOLMOSA-N
TEM
Query on TEM

Download Ideal Coordinates CCD File 
D [auth A]N-(2-HYDROXY-4-OXO-BUTYL)-N-(3-OXO-TRANSPROPENYL)AMINE
C7 H11 N O3
FXITUJNZFYVSNC-RCYFRSRISA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Observed: 0.179 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.1α = 90
b = 88β = 90
c = 141.3γ = 90
Software Package:
Software NamePurpose
PROLSQrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1994-01-31
    Type: Initial release
  • Version 1.1: 2008-03-10
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance