1b3a

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Revision as of 16:18, 28 August 2019

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

Structural highlights

1b3a is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CCL5_HUMAN] Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. Binds to CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Capoulade-Metay C, Ayouba A, Kfutwah A, Lole K, Petres S, Dudoit Y, Deterre P, Menu E, Barre-Sinoussi F, Debre P, Theodorou I. A natural CCL5/RANTES variant antagonist for CCR1 and CCR3. Immunogenetics. 2006 Jul;58(7):533-41. Epub 2006 Jun 22. PMID:16791620 doi:http://dx.doi.org/10.1007/s00251-006-0133-2
↑ Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587-92. PMID:1380064
↑ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811-5. PMID:8525373
↑ Proost P, De Meester I, Schols D, Struyf S, Lambeir AM, Wuyts A, Opdenakker G, De Clercq E, Scharpe S, Van Damme J. Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J Biol Chem. 1998 Mar 27;273(13):7222-7. PMID:9516414
↑ Lim JK, Burns JM, Lu W, DeVico AL. Multiple pathways of amino terminal processing produce two truncated variants of RANTES/CCL5. J Leukoc Biol. 2005 Aug;78(2):442-52. Epub 2005 May 27. PMID:15923218 doi:http://dx.doi.org/jlb.0305161
↑ Wilken J, Hoover D, Thompson DA, Barlow PN, McSparron H, Picard L, Wlodawer A, Lubkowski J, Kent SB. Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES. Chem Biol. 1999 Jan;6(1):43-51. PMID:9889151 doi:10.1016/S1074-5521(99)80019-2

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1b3a"

@@ Line 1: / Line 1: @@
 ==TOTAL CHEMICAL SYNTHESIS AND HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE POTENT ANTI-HIV PROTEIN AOP-RANTES==
-<StructureSection load='1b3a' size='340' side='right' caption='[[1b3a]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='1b3a' size='340' side='right'caption='[[1b3a]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1b3a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B3A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1B3A FirstGlance]. <br>
@@ Line 13: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/1b3a_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/1b3a_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 32: / Line 32: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Barlow, P N]]
 [[Category: Hoover, D]]

1b3a

From Proteopedia

Revision as of 16:18, 28 August 2019

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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