6TGI

Crystal structure of VIM-2 in complex with triazole-based inhibitor OP24


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.180 

wwPDB Validation 3D Report Full Report



Literature

Virtual screening identifies broad-spectrum beta-lactamase inhibitors with activity on clinically relevant serine- and metallo-carbapenemases.

Spyrakis, F.Santucci, M.Maso, L.Cross, S.Gianquinto, E.Sannio, F.Verdirosa, F.De Luca, F.Docquier, J.D.Cendron, L.Tondi, D.Venturelli, A.Cruciani, G.Costi, M.P.

(2020) Sci Rep 10: 12763-12763

  • DOI: 10.1038/s41598-020-69431-y
  • Primary Citation of Related Structures:  
    6TGD, 6TGI

  • PubMed Abstract: 
  • Bacteria are known to evade β-lactam antibiotic action by producing β-lactamases (BLs), including carbapenemases, which are able to hydrolyze nearly all available β-lactams. The production of BLs represents one of the best known and most targeted mec ...

    Bacteria are known to evade β-lactam antibiotic action by producing β-lactamases (BLs), including carbapenemases, which are able to hydrolyze nearly all available β-lactams. The production of BLs represents one of the best known and most targeted mechanisms of resistance in bacteria. We have performed the parallel screening of commercially available compounds against a panel of clinically relevant BLs: class A CTX-M-15 and KPC-2, subclass B1 NDM-1 and VIM-2 MBLs, and the class C P. aeruginosa AmpC. The results show that all BLs prefer scaffolds having electron pair donors: KPC-2 is preferentially inhibited by sulfonamide and tetrazole-based derivatives, NDM-1 by compounds bearing a thiol, a thiosemicarbazide or thiosemicarbazone moiety, while VIM-2 by triazole-containing molecules. Few broad-spectrum BLs inhibitors were identified; among these, compound 40 potentiates imipenem activity against an NDM-1-producing E. coli clinical strain. The binary complexes of the two most promising compounds binding NDM-1 and VIM-2 were obtained at high resolution, providing strong insights to improve molecular docking simulations, especially regarding the interaction of MBLs with inhibitors.


    Organizational Affiliation

    Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy. mariapaola.costi@unimore.it.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Vim-1AB246Pseudomonas aeruginosaMutation(s): 0 
Gene Names: blmNCTC13437_04762
EC: 3.5.2.6
Find proteins for A0A485HTJ5 (Pseudomonas aeruginosa)
Explore A0A485HTJ5 
Go to UniProtKB:  A0A485HTJ5
Protein Feature View
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
N8Z
Query on N8Z

Download CCD File 
A, B
5-(4-chloranyl-1,5-dimethyl-pyrazol-3-yl)-4-ethyl-1,2,4-triazole-3-thiol
C9 H12 Cl N5 S
JETJARLUFXKWGL-UHFFFAOYSA-N
 Ligand Interaction
ZN
Query on ZN

Download CCD File 
A, B
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
FMT
Query on FMT

Download CCD File 
A, B
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.180 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.618α = 90
b = 79.06β = 131.17
c = 68.207γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
European Communitys Seventh Framework ProgrammeItaly286998

Revision History 

  • Version 1.0: 2020-10-14
    Type: Initial release