6BC3

Cryo X-ray structure of sisomicin bound AAC-VIa


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.190 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad.

Kumar, P.Serpersu, E.H.Cuneo, M.J.

(2018) Sci Adv 4: eaas8667-eaas8667

  • DOI: https://doi.org/10.1126/sciadv.aas8667
  • Primary Citation of Related Structures:  
    6BBR, 6BBZ, 6BC2, 6BC3, 6BC4, 6BC5, 6BC6, 6BC7

  • PubMed Abstract: 

    One group of enzymes that confer resistance to aminoglycoside antibiotics through covalent modification belongs to the GCN5-related N -acetyltransferase (GNAT) superfamily. We show how a unique GNAT subfamily member uses a previously unidentified noncanonical catalytic triad, consisting of a glutamic acid, a histidine, and the antibiotic substrate itself, which acts as a nucleophile and attacks the acetyl donor molecule. Neutron diffraction studies allow for unambiguous identification of a low-barrier hydrogen bond, predicted in canonical catalytic triads to increase basicity of the histidine. This work highlights the role of this unique catalytic triad in mediating antibiotic resistance while providing new insights into the design of the next generation of aminoglycosides.


  • Organizational Affiliation

    University of Tennessee-Oak Ridge National Laboratory Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN 37996, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AAC 3-VI protein302Enterobacter cloacaeMutation(s): 0 
Gene Names: aac 3-VI
EC: 2.3.1
UniProt
Find proteins for Q47030 (Enterobacter cloacae)
Explore Q47030 
Go to UniProtKB:  Q47030
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ47030
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
COA
Query on COA

Download Ideal Coordinates CCD File 
B [auth A]COENZYME A
C21 H36 N7 O16 P3 S
RGJOEKWQDUBAIZ-IBOSZNHHSA-N
SIS
Query on SIS

Download Ideal Coordinates CCD File 
C [auth A](1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl 3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside
C19 H37 N5 O7
URWAJWIAIPFPJE-YFMIWBNJSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.190 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.534α = 90
b = 77.534β = 90
c = 83.89γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-3000data reduction
HKL-3000phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-28
    Type: Initial release
  • Version 1.1: 2018-09-12
    Changes: Data collection, Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description