4OAK

Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine-D-Alanine and copper (II)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural basis for the evolution of vancomycin resistance D,D-peptidases.

Meziane-Cherif, D.Stogios, P.J.Evdokimova, E.Savchenko, A.Courvalin, P.

(2014) Proc Natl Acad Sci U S A 111: 5872-5877

  • DOI: https://doi.org/10.1073/pnas.1402259111
  • Primary Citation of Related Structures:  
    4F78, 4MUQ, 4MUR, 4MUS, 4MUT, 4OAK

  • PubMed Abstract: 

    Vancomycin resistance in Gram-positive bacteria is due to production of cell-wall precursors ending in D-Ala-D-Lac or D-Ala-D-Ser, to which vancomycin exhibits low binding affinities, and to the elimination of the high-affinity precursors ending in D-Ala-D-Ala. Depletion of the susceptible high-affinity precursors is catalyzed by the zinc-dependent D,D-peptidases VanX and VanY acting on dipeptide (D-Ala-D-Ala) or pentapeptide (UDP-MurNac-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala), respectively. Some of the vancomycin resistance operons encode VanXY D,D-carboxypeptidase, which hydrolyzes both di- and pentapeptide. The molecular basis for the diverse specificity of Van D,D-peptidases remains unknown. We present the crystal structures of VanXYC and VanXYG in apo and transition state analog-bound forms and of VanXYC in complex with the D-Ala-D-Ala substrate and D-Ala product. Structural and biochemical analysis identified the molecular determinants of VanXY dual specificity. VanXY residues 110-115 form a mobile cap over the catalytic site, whose flexibility is involved in the switch between di- and pentapeptide hydrolysis. Structure-based alignment of the Van D,D-peptidases showed that VanY enzymes lack this element, which promotes binding of the penta- rather than that of the dipeptide. The structures also highlight the molecular basis for selection of D-Ala-ending precursors over the modified resistance targets. These results illustrate the remarkable adaptability of the D,D-peptidase fold in response to antibiotic pressure via evolution of specific structural elements that confer hydrolytic activity against vancomycin-susceptible peptidoglycan precursors.


  • Organizational Affiliation

    Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
D,D-dipeptidase/D,D-carboxypeptidase
A, B
211Enterococcus gallinarumMutation(s): 1 
Gene Names: vanXYc
UniProt
Find proteins for Q9JN36 (Enterococcus gallinarum)
Explore Q9JN36 
Go to UniProtKB:  Q9JN36
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9JN36
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PE3
Query on PE3

Download Ideal Coordinates CCD File 
L [auth A],
M [auth A],
U [auth B],
V [auth B]
3,6,9,12,15,18,21,24,27,30,33,36,39-TRIDECAOXAHENTETRACONTANE-1,41-DIOL
C28 H58 O15
ILLKMACMBHTSHP-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A],
Q [auth B],
R [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
DAL
Query on DAL

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
O [auth B],
P [auth B]
D-ALANINE
C3 H7 N O2
QNAYBMKLOCPYGJ-UWTATZPHSA-N
CU
Query on CU

Download Ideal Coordinates CCD File 
C [auth A],
N [auth B]
COPPER (II) ION
Cu
JPVYNHNXODAKFH-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
J [auth A]
K [auth A]
S [auth B]
H [auth A],
I [auth A],
J [auth A],
K [auth A],
S [auth B],
T [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG
Query on MG

Download Ideal Coordinates CCD File 
G [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 
  • Space Group: P 1
  • Diffraction Data: https://doi.org/10.18430/M34OAK
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.939α = 80.53
b = 43.083β = 74.52
c = 66.316γ = 64.01
Software Package:
Software NamePurpose
CrystalCleardata collection
PHENIXmodel building
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2014-01-15
    Type: Initial release
  • Version 1.1: 2014-01-29
    Changes: Other
  • Version 1.2: 2014-04-23
    Changes: Database references
  • Version 1.3: 2014-05-14
    Changes: Database references
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description