3G31

CTX-M-9 class A beta-lactamase complexed with compound 4 (GF1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.170 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Molecular docking and ligand specificity in fragment-based inhibitor discovery

Chen, Y.Shoichet, B.K.

(2009) Nat Chem Biol 5: 358-364

  • DOI: https://doi.org/10.1038/nchembio.155
  • Primary Citation of Related Structures:  
    3G2Y, 3G2Z, 3G30, 3G31, 3G32, 3G34, 3G35

  • PubMed Abstract: 

    Fragment screens have successfully identified new scaffolds in drug discovery, often with relatively high hit rates (5%) using small screening libraries (1,000-10,000 compounds). This raises two questions: would other noteworthy chemotypes be found were one to screen all commercially available fragments (>300,000), and does the success rate imply low specificity of fragments? We used molecular docking to screen large libraries of fragments against CTX-M beta-lactamase. We identified ten millimolar-range inhibitors from the 69 compounds tested. The docking poses corresponded closely to the crystallographic structures subsequently determined. Notably, these initial low-affinity hits showed little specificity between CTX-M and an unrelated beta-lactamase, AmpC, which is unusual among beta-lactamase inhibitors. This is consistent with the idea that the high hit rates among fragments correlate to a low initial specificity. As the inhibitors were progressed, both specificity and affinity rose together, yielding to our knowledge the first micromolar-range noncovalent inhibitors against a class A beta-lactamase.


  • Organizational Affiliation

    Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-lactamase CTX-M-9a
A, B
263Escherichia coliMutation(s): 0 
Gene Names: blaCTX-M-9blaCTX-M-9aCTX-M
EC: 3.5.2.6
UniProt
Find proteins for Q9L5C8 (Escherichia coli)
Explore Q9L5C8 
Go to UniProtKB:  Q9L5C8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9L5C8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GF1
Query on GF1

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A],
I [auth B],
J [auth B]
(2S)-2-[(3aR,4R,7S,7aS)-1,3-dioxooctahydro-2H-4,7-methanoisoindol-2-yl]propanoic acid
C12 H15 N O4
REFMTLIXGKZVDF-VRGHQRLXSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
F [auth A],
K [auth B]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
DMS
Query on DMS

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
L [auth B]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
GF1 Binding MOAD:  3G31 Ki: 1.30e+6 (nM) from 1 assay(s)
PDBBind:  3G31 Ki: 1.30e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.170 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.279α = 90
b = 106.765β = 101.74
c = 47.777γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-03-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description