1b3a

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(New page: 200px<br /> <applet load="1b3a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b3a, resolution 1.6&Aring;" /> '''TOTAL CHEMICAL SYNTH...)
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Revision as of 11:46, 8 November 2007


1b3a, resolution 1.6Å

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TOTAL CHEMICAL SYNTHESIS AND HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE POTENT ANTI-HIV PROTEIN AOP-RANTES

Overview

BACKGROUND: RANTES is a CC-type chemokine protein that acts as a, chemoattractant for several kinds of leukocytes, playing an important, pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1), into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and, inhibits HIV-1 entry into peripheral blood cells. Interaction with, chemokine receptors involves a distinct set of residues at the amino, terminus of RANTES. This finding was utilized in the development of a, chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that, was originally produced from the recombinant protein using semisynthetic, methods. RESULTS: AOP-RANTES has been produced by a novel total chemical, synthesis that provides efficient, direct access to large amounts of this, anti-HIV protein analog. The crystal structure of chemically synthesized, AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is, a dimer, with the amino-terminal pentane oxime moiety clearly defined., CONCLUSIONS: Total chemical synthesis of AOP-RANTES provides a convenient, method of producing the multi-milligram quantities of this protein needed, to investigate the molecular basis of receptor binding and antiviral, activity. This work provides the first truly high-resolution structure of, a RANTES protein, although the structure of RANTES was known from previous, nuclear magnetic resonance (NMR) determinations.

About this Structure

1B3A is a Single protein structure of sequence from [1] with SO4 and AOP as ligands. Full crystallographic information is available from OCA.

Reference

Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES., Wilken J, Hoover D, Thompson DA, Barlow PN, McSparron H, Picard L, Wlodawer A, Lubkowski J, Kent SB, Chem Biol. 1999 Jan;6(1):43-51. PMID:9889151

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