6MN5

Crystal structure of aminoglycoside acetyltransferase AAC(3)-IVa, H154A mutant, in complex with gentamicin C1A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.58 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.187 

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This is version 1.3 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, AAC(3)-IVa
A, B, C, D, E
A, B, C, D, E, F
262Escherichia coliMutation(s): 1 
Gene Names: 
EC: 2.3.1.81
UniProt
Find proteins for Q306W4 (Escherichia coli)
Explore Q306W4 
Go to UniProtKB:  Q306W4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ306W4
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 
JA [auth B],
NB [auth D],
YA [auth C]
3,6,9,12,15,18,21,24,27,30,33,36,39-TRIDECAOXAHENTETRACONTANE-1,41-DIOL
C28 H58 O15
ILLKMACMBHTSHP-UHFFFAOYSA-N
LLL
Query on LLL

Download Ideal Coordinates CCD File 
G [auth A]
KA [auth C]
OB [auth E]
W [auth B]
WB [auth F]
G [auth A],
KA [auth C],
OB [auth E],
W [auth B],
WB [auth F],
ZA [auth D]
(2R,3R,4R,5R)-2-((1S,2S,3R,4S,6R)-4,6-DIAMINO-3-((2R,3R,6S)-3-AMINO-6-(AMINOMETHYL)-TETRAHYDRO-2H-PYRAN-2-YLOXY)-2-HYDR OXYCYCLOHEXYLOXY)-5-METHYL-4-(METHYLAMINO)-TETRAHYDRO-2H-PYRAN-3,5-DIOL
C19 H39 N5 O7
VEGXETMJINRLTH-BOZYPMBZSA-N
EPE
Query on EPE

Download Ideal Coordinates CCD File 
BB [auth D]
CB [auth D]
I [auth A]
J [auth A]
MA [auth C]
BB [auth D],
CB [auth D],
I [auth A],
J [auth A],
MA [auth C],
NA [auth C],
QB [auth E],
RB [auth E],
Y [auth B],
YB [auth F],
Z [auth B],
ZB [auth F]
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
AA [auth B],
DB [auth D],
EB [auth D],
K [auth A],
OA [auth C]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
AB [auth D]
H [auth A]
LA [auth C]
PB [auth E]
X [auth B]
AB [auth D],
H [auth A],
LA [auth C],
PB [auth E],
X [auth B],
XB [auth F]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
AC [auth F]
BA [auth B]
CA [auth B]
DA [auth B]
EA [auth B]
AC [auth F],
BA [auth B],
CA [auth B],
DA [auth B],
EA [auth B],
FA [auth B],
FB [auth D],
GA [auth B],
GB [auth D],
HA [auth B],
HB [auth D],
IA [auth B],
IB [auth D],
JB [auth D],
KB [auth D],
L [auth A],
LB [auth D],
M [auth A],
MB [auth D],
N [auth A],
O [auth A],
P [auth A],
PA [auth C],
Q [auth A],
QA [auth C],
R [auth A],
RA [auth C],
S [auth A],
SA [auth C],
SB [auth E],
T [auth A],
TA [auth C],
TB [auth E],
U [auth A],
UA [auth C],
UB [auth E],
V [auth A],
VA [auth C],
VB [auth E],
WA [auth C],
XA [auth C]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.58 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.187 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.609α = 90
b = 131.881β = 90
c = 266.872γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing
PHENIXmodel building
Cootmodel building

Structure Validation

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Entry History & Funding Information

Deposition Data


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

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: 2022-04-06
    Changes: Database references, Derived calculations, Structure summary
  • Version 1.3: 2023-10-11
    Changes: Data collection, Refinement description