5N0H

Crystal structure of NDM-1 in complex with hydrolyzed meropenem - new refinement


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.155 
  • R-Value Observed: 0.157 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history

Re-refinement Note

This entry reflects an alternative modeling of the original data in: 4eyl


Literature

A close look onto structural models and primary ligands of metallo-beta-lactamases.

Raczynska, J.E.Shabalin, I.G.Minor, W.Wlodawer, A.Jaskolski, M.

(2018) Drug Resist Updat 40: 1-12

  • DOI: https://doi.org/10.1016/j.drup.2018.08.001
  • Primary Citation of Related Structures:  
    5N0H, 5N0I, 5NBK, 5O2E, 5O2F, 5W8W, 6EX7

  • PubMed Abstract: 

    β-Lactamases are hydrolytic enzymes capable of opening the β-lactam ring of antibiotics such as penicillin, thus endowing the bacteria that produce them with antibiotic resistance. Of particular medical concern are metallo-β-lactamases (MBLs), with an active site built around coordinated Zn cations. MBLs are pan-reactive enzymes that can break down almost all classes of β-lactams, including such last-resort antibiotics as carbapenems. They are not only broad-spectrum-reactive but are often plasmid-borne (e.g., the New Delhi enzyme, NDM), and can spread horizontally even among unrelated bacteria. Acquired MBLs are encoded by mobile genetic elements, which often include other resistance genes, making the microbiological situation particularly alarming. There is an urgent need to develop MBL inhibitors in order to rescue our antibiotic armory. A number of such efforts have been undertaken, most notably using the 3D structures of various MBLs as drug-design targets. Structure-guided drug discovery depends on the quality of the structures that are collected in the Protein Data Bank (PDB) and on the consistency of the information in dedicated β-lactamase databases. We conducted a careful review of the crystal structures of class B β-lactamases, concluding that the quality of these structures varies widely, especially in the regions where small molecules interact with the macromolecules. In a number of examples the interpretation of the bound ligands (e.g., inhibitors, substrate/product analogs) is doubtful or even incorrect, and it appears that in some cases the modeling of ligands was not supported by electron density. For ten MBL structures, alternative interpretations of the original diffraction data could be proposed and the new models have been deposited in the PDB. In four cases, these models, prepared jointly with the authors of the original depositions, superseded the previous deposits. This review emphasizes the importance of critical assessment of structural models describing key drug design targets at the level of the raw experimental data. Since the structures reviewed here are the basis for ongoing design of new MBL inhibitors, it is important to identify and correct the problems with ambiguous crystallographic interpretations, thus enhancing reproducibility in this highly medically relevant area.


  • Organizational Affiliation

    Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Metallo-beta-lactamase type 2
A, B
245Klebsiella 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
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8YL
Query on 8YL

Download Ideal Coordinates CCD File 
C [auth A](2S,3R)-2-[(2S,3R)-1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-4-[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfan yl-3-methyl-2,3-dihydro-1H-pyrrole-5-carboxylic acid
C17 H27 N3 O6 S
ILVWWUFTACAPIZ-PQTSNVLCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
H [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
K [auth B],
L [auth B],
M [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
I [auth B],
J [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.155 
  • R-Value Observed: 0.157 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106α = 90
b = 106β = 90
c = 92.58γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Center for Research and DevelopmentPoland--

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-05
    Type: Initial release
  • Version 2.0: 2017-12-13
    Changes: Advisory, Atomic model, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2018-12-26
    Changes: Data collection, Database references
  • Version 2.2: 2019-10-16
    Changes: Data collection