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1b3a
From Proteopedia
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| - | [[Image:1b3a.gif|left|200px]]<br /> | + | [[Image:1b3a.gif|left|200px]]<br /><applet load="1b3a" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1b3a" size=" | + | |
caption="1b3a, resolution 1.6Å" /> | caption="1b3a, resolution 1.6Å" /> | ||
'''TOTAL CHEMICAL SYNTHESIS AND HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE POTENT ANTI-HIV PROTEIN AOP-RANTES'''<br /> | '''TOTAL CHEMICAL SYNTHESIS AND HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE POTENT ANTI-HIV PROTEIN AOP-RANTES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: RANTES is a CC-type chemokine protein that acts as a | + | 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. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1B3A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with SO4 and AOP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1B3A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=AOP:'>AOP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B3A OCA]. |
==Reference== | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9889151 9889151] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9889151 9889151] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barlow, P | + | [[Category: Barlow, P N.]] |
[[Category: Hoover, D.]] | [[Category: Hoover, D.]] | ||
| - | [[Category: Kent, S | + | [[Category: Kent, S B.H.]] |
[[Category: Lubkowski, J.]] | [[Category: Lubkowski, J.]] | ||
[[Category: Mcsparron, H.]] | [[Category: Mcsparron, H.]] | ||
[[Category: Picard, L.]] | [[Category: Picard, L.]] | ||
| - | [[Category: Thompson, D | + | [[Category: Thompson, D A.]] |
[[Category: Wilken, J.]] | [[Category: Wilken, J.]] | ||
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
| Line 33: | Line 32: | ||
[[Category: rantes]] | [[Category: rantes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:03 2008'' |
Revision as of 09:51, 21 February 2008
|
TOTAL CHEMICAL SYNTHESIS AND HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE POTENT ANTI-HIV PROTEIN AOP-RANTES
Contents |
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.
Disease
Known diseases associated with this structure: HIV-1 disease, delayed progression of OMIM:[187011], HIV-1 disease, rapid progression of OMIM:[187011]
About this Structure
1B3A is a Single protein structure of sequence from [1] with and 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
Page seeded by OCA on Thu Feb 21 11:51:03 2008
Categories: Single protein | Barlow, P N. | Hoover, D. | Kent, S B.H. | Lubkowski, J. | Mcsparron, H. | Picard, L. | Thompson, D A. | Wilken, J. | Wlodawer, A. | AOP | SO4 | Chemical protein synthesis | Chemokine | Crystal structure | Hiv-1 | Rantes
