RCSB PDB - 6Q2Y: Crystal structure of NDM-1 beta-lactamase in complex with broad spectrum boronic inhibitor cpd3

 6Q2Y

Crystal structure of NDM-1 beta-lactamase in complex with broad spectrum boronic inhibitor cpd3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.176 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.166 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

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This is version 1.2 of the entry. See complete history


Literature

X-ray Crystallography Deciphers the Activity of Broad-Spectrum Boronic Acid beta-Lactamase Inhibitors.

Cendron, L.Quotadamo, A.Maso, L.Bellio, P.Montanari, M.Celenza, G.Venturelli, A.Costi, M.P.Tondi, D.

(2019) ACS Med Chem Lett 10: 650-655

  • DOI: https://doi.org/10.1021/acsmedchemlett.8b00607
  • Primary Citation of Related Structures:  
    6IBS, 6IBV, 6Q2Y, 6Q30, 6Q35

  • PubMed Abstract: 

    Recent decades have witnessed a dramatic increase of multidrug resistant (MDR) bacteria, compromising the efficacy of available antibiotics, and a continual decline in the discovery of novel antibacterials. We recently reported the first library of benzo[b]thiophen-2-ylboronic acid inhibitors sharing broad spectrum activity against β-lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of β-lactamases has been here structurally investigated. An extensive X-ray crystallographic analysis of boronic acids (BAs) binding to proteins representative of serine BLs (SBLs) and metallo β-lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recognition, especially in the interaction with MBLs. Our derivatives are the first case of noncyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.


  • Organizational Affiliation

    Department of Biology, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Metallo-beta-lactamase type 2
A, B
244Klebsiella pneumoniaeMutation(s): 0 
Gene Names: blaNDM-1
EC: 3.5.2.6
UniProt
Find proteins for C7C422 (Klebsiella pneumoniae)
Explore C7C422 
Go to UniProtKB:  C7C422
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupC7C422
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EPE
Query on EPE

Download Ideal Coordinates CCD File 
M [auth B]4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
HCQ
Query on HCQ

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]
[5-(aminomethyl)-1-benzothiophen-2-yl]-tris(oxidanyl)boranuide
C9 H11 B N O3 S
MOEIXULQWWCKOY-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth B],
I [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
J [auth B],
K [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.176 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.166 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.425α = 90
b = 73.95β = 90
c = 77.687γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
xia2data reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted HCQClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
European Communitys Seventh Framework ProgrammeItaly286998

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-24
    Type: Initial release
  • Version 1.1: 2019-05-01
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Derived calculations, Refinement description