4JD6

Crystal structure of Mycobacterium tuberculosis Eis in complex with coenzyme A and tobramycin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.246 

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This is version 1.2 of the entry. See complete history


Literature

Chemical and structural insights into the regioversatility of the aminoglycoside acetyltransferase eis.

Houghton, J.L.Biswas, T.Chen, W.Tsodikov, O.V.Garneau-Tsodikova, S.

(2013) Chembiochem 14: 2127-2135

  • DOI: https://doi.org/10.1002/cbic.201300359
  • Primary Citation of Related Structures:  
    4JD6

  • PubMed Abstract: 

    A recently discovered cause of tuberculosis resistance to a drug of last resort, the aminoglycoside kanamycin, results from modification of this drug by the enhanced intracellular survival (Eis) protein. Eis is a structurally and functionally unique acetyltransferase with an unusual capability of acetylating aminoglycosides at multiple positions. The extent of this regioversatility and its defining protein features are unclear. Herein, we determined the positions and order of acetylation of five aminoglycosides by NMR spectroscopy. This analysis revealed unprecedented acetylation of the 3''-amine of kanamycin, amikacin, and tobramycin, and the γ-amine of the 4-amino-2-hydroxybutyryl group of amikacin. A crystal structure of Eis in complex with coenzyme A and tobramycin revealed how tobramycin can be accommodated in the Eis active site in two binding modes, consistent with its diacetylation. These studies, describing chemical and structural details of acetylation, will guide future efforts towards designing aminoglycosides and Eis inhibitors to overcome resistance in tuberculosis.


  • Organizational Affiliation

    Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109 (USA); Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 (USA).


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Enhanced intracellular survival protein
A, B, C, D, E
A, B, C, D, E, F
428Mycobacterium tuberculosis H37RvMutation(s): 1 
Gene Names: RVBD_2416c
UniProt
Find proteins for P9WFK7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WFK7 
Go to UniProtKB:  P9WFK7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WFK7
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.246 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.226α = 90
b = 154.908β = 104.7
c = 115.286γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-23
    Type: Initial release
  • Version 1.1: 2014-03-19
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations