9IXP

Crystal structure of OXA-10 variant A124T


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural insights into alterations in the substrate spectrum of serine-beta-lactamase OXA-10 from Pseudomonas aeruginosa by single amino acid substitutions.

Lee, C.E.Park, Y.Park, H.Kwak, K.Lee, H.Yun, J.Lee, D.Lee, J.H.Lee, S.H.Kang, L.W.

(2024) Emerg Microbes Infect 13: 2412631-2412631

  • DOI: https://doi.org/10.1080/22221751.2024.2412631
  • Primary Citation of Related Structures:  
    9IXN, 9IXO, 9IXP, 9IXQ, 9IXR

  • PubMed Abstract: 

    The extensive use of β-lactam antibiotics has led to significant resistance, primarily due to hydrolysis by β-lactamases. OXA class D β-lactamases can hydrolyze a wide range of β-lactam antibiotics, rendering many treatments ineffective. We investigated the effects of single amino acid substitutions in OXA-10 on its substrate spectrum. Broad-spectrum variants with point mutations were searched and biochemically verified. Three key residues, G157D, A124T, and N73S, were confirmed in the variants, and their crystal structures were determined. Based on an enzyme kinetics study, the hydrolytic activity against broad-spectrum cephalosporins, particularly ceftazidime, was significantly enhanced by the G157D mutation in loop 2. The A124T or N73S mutation close to loop 2 also resulted in higher ceftazidime activity. All structures of variants with point mutations in loop 2 or nearby exhibited increased loop 2 flexibility, which facilitated the binding of ceftazidime. These results highlight the effect of a single amino acid substitution in OXA-10 on broad-spectrum drug resistance. Structure-activity relationship studies will help us understand the drug resistance spectrum of β-lactamases, enhance the effectiveness of existing β-lactam antibiotics, and develop new drugs.


  • Organizational Affiliation

    Department of Biological Sciences, Konkuk University, Seoul, South Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-lactamase OXA-10
A, B
248Pseudomonas aeruginosaMutation(s): 1 
Gene Names: blaoxa10pse2
EC: 3.5.2.6
UniProt
Find proteins for Q6QJ55 (Pseudomonas aeruginosa)
Explore Q6QJ55 
Go to UniProtKB:  Q6QJ55
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6QJ55
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
KCX
Query on KCX
A, B
L-PEPTIDE LINKINGC7 H14 N2 O4LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.726α = 90
b = 102.44β = 90
c = 127.542γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
HKL-3000phasing
PDB_EXTRACTdata extraction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Research Foundation (NRF, Korea)Korea, Republic Of2017M3A9E4078017

Revision History  (Full details and data files)

  • Version 1.0: 2024-10-23
    Type: Initial release
  • Version 1.1: 2024-11-06
    Changes: Database references