2HW2

Crystal structure of Rifampin ADP-ribosyl transferase in complex with Rifampin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.134 
  • R-Value Observed: 0.137 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr.

Baysarowich, J.Koteva, K.Hughes, D.W.Ejim, L.Griffiths, E.Zhang, K.Junop, M.Wright, G.D.

(2008) Proc Natl Acad Sci U S A 105: 4886-4891

  • DOI: https://doi.org/10.1073/pnas.0711939105
  • Primary Citation of Related Structures:  
    2HW2

  • PubMed Abstract: 

    The rifamycin antibiotic rifampin is important for the treatment of tuberculosis and infections caused by multidrug-resistant Staphylococcus aureus. Recent iterations of the rifampin core structure have resulted in new drugs and drug candidates for the treatment of a much broader range of infectious diseases. This expanded use of rifamycin antibiotics has the potential to select for increased resistance. One poorly characterized mechanism of resistance is through Arr enzymes that catalyze ADP-ribosylation of rifamycins. We find that genes encoding predicted Arr enzymes are widely distributed in the genomes of pathogenic and nonpathogenic bacteria. Biochemical analysis of three representative Arr enzymes from environmental and pathogenic bacterial sources shows that these have equally efficient drug resistance capacity in vitro and in vivo. The 3D structure of one of these orthologues from Mycobacterium smegmatis was determined and reveals structural homology with ADP-ribosyltransferases important in eukaryotic biology, including poly(ADP-ribose) polymerases (PARPs) and bacterial toxins, despite no significant amino acid sequence homology with these proteins. This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic.


  • Organizational Affiliation

    M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Rifampin ADP-ribosyl transferase143Mycolicibacterium smegmatisMutation(s): 1 
Gene Names: arr
EC: 2.4.2.30
UniProt
Find proteins for A0QRS5 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0QRS5 
Go to UniProtKB:  A0QRS5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0QRS5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
RFP Binding MOAD:  2HW2 Ki: 1.07e+6 (nM) from 1 assay(s)
PDBBind:  2HW2 Ki: 1.07e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.134 
  • R-Value Observed: 0.137 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.663α = 90
b = 61.041β = 91.81
c = 45.567γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-07-31
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-04-11
    Changes: Other
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-14
    Changes: Data collection