2VXW

Structural and Functional Studies of the Potent Anti-HIV Chemokine Variant P2-RANTES


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 

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This is version 1.1 of the entry. See complete history


Literature

Structural and Functional Studies of the Potent Anti-HIV Chemokine Variant P2-Rantes.

Jin, H.Kagiampakis, I.Li, P.Liwang, P.J.

(2010) Proteins 78: 295

  • DOI: https://doi.org/10.1002/prot.22542
  • Primary Citation of Related Structures:  
    2VXW

  • PubMed Abstract: 

    The N-terminal region of the chemokine RANTES is critical for its function. A synthesized N-terminally modified analog of RANTES, P2-RANTES, was discovered using a phage display selection against living CCR5-expressing cells, and has been reported to inhibit HIV-1 env-mediated cell-cell fusion at subnanomolar levels (Hartley et al. J Virol 2003;77:6637-6644). In the present study we produced this protein using E. coli overexpression and extensively studied its structure and function. The x-ray crystal structure of P2-RANTES was solved and refined at 1.7 A resolution. This protein was found to be predominantly a monomer in solution by analytical ultracentrifugation, but a tetramer in the crystal. In studies of glycosaminoglycan binding, P2-RANTES was found to be significantly less able to bind heparin than wild type RANTES. We also tested this protein for receptor internalization where it was shown to be functional, in cell-cell fusion assays where recombinant P2-RANTES was a potent fusion inhibitor (IC(50) = 2.4 +/- 0.8 nM), and in single round infection assays where P2-RANTES inhibited at subnanomolar levels. Further, in a modified fusion assay designed to test specificity of inhibition, P2-RANTES was also highly effective, with a 65-fold improvement over the fusion inhibitor C37, which is closely related to the clinically approved inhibitor T-20. These studies provide detailed structural and functional information for this novel N-terminally modified chemokine mutant. This information will be very useful in the development of more potent anti-HIV agents. PDB Accession Number: 2vxw.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
C-C MOTIF CHEMOKINE 5
A, B, C, D
69Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P13501 (Homo sapiens)
Explore P13501 
Go to UniProtKB:  P13501
PHAROS:  P13501
GTEx:  ENSG00000271503 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP13501
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.678α = 90
b = 51.982β = 117.87
c = 61.692γ = 90
Software Package:
Software NamePurpose
CNSrefinement
CNSdata reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-29
    Type: Initial release
  • Version 1.1: 2012-08-22
    Changes: Advisory, Version format compliance