4JMI

Sec7 domain of ARNO, an exchange factor, at 1.5 Angstrom resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.166 
  • R-Value Work: 0.133 
  • R-Value Observed: 0.135 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Fragment-based identification of a locus in the Sec7 domain of Arno for the design of protein-protein interaction inhibitors

Rouhana, J.Hoh, F.Estaran, S.Henriquet, C.Boublik, Y.Kerkour, A.Trouillard, R.Martinez, J.Pugniere, M.Padilla, A.Chavanieu, A.

(2013) J Med Chem 56: 8497-8511

  • DOI: https://doi.org/10.1021/jm4009357
  • Primary Citation of Related Structures:  
    4JMI, 4JMO, 4JWL, 4JXH, 4L5M

  • PubMed Abstract: 

    By virtual screening using a fragment-based drug design (FBDD) approach, 33 fragments were selected within small pockets around interaction hot spots on the Sec7 surface of the nucleotide exchange factor Arno, and then their ability to interfere with the Arno-catalyzed nucleotide exchange on the G-protein Arf1 was evaluated. By use of SPR, NMR, and fluorescence assays, the direct binding of three of the identified fragments to Arno Sec7 domain was demonstrated and the promiscuous aggregate behavior evaluated. Then the binding mode of one fragment and of a more active analogue was solved by X-ray crystallography. This highlighted the role of stable and transient pockets at the Sec7 domain surface in the discovery and binding of interfering compounds. These results provide structural information on how small organic compounds can interfere with the Arf1-Arno Sec7 domain interaction and may guide the rational drug design of competitive inhibitors of Arno enzymatic activity.


  • Organizational Affiliation

    Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Universités Montpellier 1 et 2, Faculté de Pharmacie, 15 Avenue Charles Flahault BP14491, 34093 Montpellier Cedex 5, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cytohesin-2200Homo sapiensMutation(s): 0 
Gene Names: CYTH2ARNOPSCD2PSCD2L
UniProt & NIH Common Fund Data Resources
Find proteins for Q99418 (Homo sapiens)
Explore Q99418 
Go to UniProtKB:  Q99418
PHAROS:  Q99418
GTEx:  ENSG00000105443 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99418
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.166 
  • R-Value Work: 0.133 
  • R-Value Observed: 0.135 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.54α = 90
b = 89.54β = 90
c = 89.54γ = 90
Software Package:
Software NamePurpose
DNAdata collection
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-23
    Type: Initial release
  • Version 1.1: 2013-10-30
    Changes: Database references
  • Version 1.2: 2013-11-06
    Changes: Structure summary
  • Version 1.3: 2014-04-23
    Changes: Database references
  • Version 1.4: 2023-11-08
    Changes: Data collection, Database references, Refinement description