6MMZ

Crystal structure of meta-AAC0038, an environmental aminoglycoside resistance enzyme, H29A mutant apoenzyme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family.

Stogios, P.J.Bordeleau, E.Xu, Z.Skarina, T.Evdokimova, E.Chou, S.Diorio-Toth, L.D'Souza, A.W.Patel, S.Dantas, G.Wright, G.D.Savchenko, A.

(2022) Commun Biol 5: 263-263

  • DOI: https://doi.org/10.1038/s42003-022-03219-w
  • Primary Citation of Related Structures:  
    5HT0, 6MMZ, 6MN0, 6MN3, 6MN4, 6MN5, 7KES, 7LAO, 7LAP

  • PubMed Abstract: 

    The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment.


  • Organizational Affiliation

    Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, M5S 3E5, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aminoglycoside N(3)-acetyltransferase
A, B, C, D, E
A, B, C, D, E, F
263uncultured bacteriumMutation(s): 1 
EC: 2.3.1.81
UniProt
Find proteins for A0A059X981 (uncultured bacterium)
Explore A0A059X981 
Go to UniProtKB:  A0A059X981
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A059X981
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
AA [auth F]
BA [auth F]
CA [auth F]
G [auth A]
H [auth A]
AA [auth F],
BA [auth F],
CA [auth F],
G [auth A],
H [auth A],
I [auth A],
J [auth B],
K [auth B],
L [auth B],
M [auth C],
N [auth C],
O [auth C],
P [auth C],
Q [auth C],
S [auth D],
T [auth D],
V [auth E],
W [auth E],
X [auth E],
Y [auth E]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
CL
Query on CL

Download Ideal Coordinates CCD File 
DA [auth F],
R [auth C],
U [auth D],
Z [auth E]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B, C, D, E
A, B, C, D, E, F
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 105.761α = 90
b = 158.124β = 94.87
c = 143.44γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing
PHENIXmodel building
Cootmodel building

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesHHSN272201200026C
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesHHSN272201700060C

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-24
    Type: Initial release
  • Version 1.1: 2019-12-18
    Changes: Author supporting evidence
  • Version 1.2: 2020-02-26
    Changes: Database references
  • Version 1.3: 2022-04-06
    Changes: Database references
  • Version 1.4: 2023-10-11
    Changes: Data collection, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection