5YPM

Crystal structure of NDM-1 bound to hydrolyzed meropenem representing an EI1 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis.

Feng, H.Liu, X.Wang, S.Fleming, J.Wang, D.C.Liu, W.

(2017) Nat Commun 8: 2242-2242

  • DOI: https://doi.org/10.1038/s41467-017-02339-w
  • Primary Citation of Related Structures:  
    5YPI, 5YPK, 5YPL, 5YPM, 5YPN

  • PubMed Abstract: 

    New Delhi metallo-β-lactamases (NDMs), the recent additions to metallo-β-lactamases (MBLs), pose a serious public health threat due to its highly efficient hydrolysis of β-lactam antibiotics and rapid worldwide dissemination. The MBL-hydrolyzing mechanism for carbapenems is less studied than that of penicillins and cephalosporins. Here, we report crystal structures of NDM-1 in complex with hydrolyzed imipenem and meropenem, at resolutions of 1.80-2.32 Å, together with NMR spectra monitoring meropenem hydrolysis. Three enzyme-intermediate/product derivatives, EI 1 , EI 2 , and EP, are trapped in these crystals. Our structural data reveal double-bond tautomerization from Δ 2 to Δ 1 , absence of a bridging water molecule and an exclusive β-diastereomeric product, all suggesting that the hydrolytic intermediates are protonated by a bulky water molecule incoming from the β-face. These results strongly suggest a distinct mechanism of NDM-1-catalyzed carbapenem hydrolysis from that of penicillin or cephalosporin hydrolysis, which may provide a novel rationale for design of mechanism-based inhibitors.


  • Organizational Affiliation

    National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Metallo-beta-lactamase NDM-1
A, B, C, D, E
A, B, C, D, E, F, G, H
242Escherichia coliMutation(s): 0 
Gene Names: blaNDM-1
UniProt
Find proteins for E5KIY2 (Escherichia coli)
Explore E5KIY2 
Go to UniProtKB:  E5KIY2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupE5KIY2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8YL
Query on 8YL

Download Ideal Coordinates CCD File 
BA [auth E]
FA [auth F]
JA [auth G]
K [auth A]
MA [auth H]
BA [auth E],
FA [auth F],
JA [auth G],
K [auth A],
MA [auth H],
O [auth B],
S [auth C],
W [auth D]
(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 
CA [auth E]
GA [auth F]
L [auth A]
P [auth B]
T [auth C]
CA [auth E],
GA [auth F],
L [auth A],
P [auth B],
T [auth C],
X [auth D],
Y [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN
Query on ZN

Download Ideal Coordinates CCD File 
AA [auth E]
DA [auth F]
EA [auth F]
HA [auth G]
I [auth A]
AA [auth E],
DA [auth F],
EA [auth F],
HA [auth G],
I [auth A],
IA [auth G],
J [auth A],
KA [auth H],
LA [auth H],
M [auth B],
N [auth B],
Q [auth C],
R [auth C],
U [auth D],
V [auth D],
Z [auth E]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.79α = 90
b = 74.02β = 90.44
c = 155.04γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-21
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary