This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
7hvp
From Proteopedia
(New page: 200px<br /> <applet load="7hvp" size="450" color="white" frame="true" align="right" spinBox="true" caption="7hvp, resolution 2.4Å" /> '''X-RAY CRYSTALLOGRAPH...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:7hvp.gif|left|200px]]<br /> | + | [[Image:7hvp.gif|left|200px]]<br /><applet load="7hvp" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="7hvp" size=" | + | |
caption="7hvp, resolution 2.4Å" /> | caption="7hvp, resolution 2.4Å" /> | ||
'''X-RAY CRYSTALLOGRAPHIC STRUCTURE OF A COMPLEX BETWEEN A SYNTHETIC PROTEASE OF HUMAN IMMUNODEFICIENCY VIRUS 1 AND A SUBSTRATE-BASED HYDROXYETHYLAMINE INHIBITOR'''<br /> | '''X-RAY CRYSTALLOGRAPHIC STRUCTURE OF A COMPLEX BETWEEN A SYNTHETIC PROTEASE OF HUMAN IMMUNODEFICIENCY VIRUS 1 AND A SUBSTRATE-BASED HYDROXYETHYLAMINE INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of a crystal complex of the chemically synthesized protease | + | The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe; the Ki is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-A resolution by using restrained least squares with rms deviations in bond lengths of 0.02 A and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365. |
==About this Structure== | ==About this Structure== | ||
| - | 7HVP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with ACE, CH2 and OME as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 7HVP with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb6_1.html HIV-1 Protease]]. Full crystallographic information is available from [http:// | + | 7HVP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=ACE:'>ACE</scene>, <scene name='pdbligand=CH2:'>CH2</scene> and <scene name='pdbligand=OME:'>OME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 7HVP with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb6_1.html HIV-1 Protease]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7HVP OCA]. |
==Reference== | ==Reference== | ||
| Line 16: | Line 15: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Green, J.]] | [[Category: Green, J.]] | ||
| - | [[Category: Kent, S | + | [[Category: Kent, S B.H.]] |
| - | [[Category: Miller, M | + | [[Category: Miller, M M.]] |
| - | [[Category: Rich, D | + | [[Category: Rich, D H.]] |
[[Category: Schneider, J.]] | [[Category: Schneider, J.]] | ||
| - | [[Category: Swain, A | + | [[Category: Swain, A L.]] |
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
| Line 27: | Line 26: | ||
[[Category: hydrolase(acid proteinase)]] | [[Category: hydrolase(acid proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:17:09 2008'' |
Revision as of 17:17, 21 February 2008
|
X-RAY CRYSTALLOGRAPHIC STRUCTURE OF A COMPLEX BETWEEN A SYNTHETIC PROTEASE OF HUMAN IMMUNODEFICIENCY VIRUS 1 AND A SUBSTRATE-BASED HYDROXYETHYLAMINE INHIBITOR
Overview
The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe; the Ki is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-A resolution by using restrained least squares with rms deviations in bond lengths of 0.02 A and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365.
About this Structure
7HVP is a Single protein structure of sequence from Human immunodeficiency virus 1 with , and as ligands. The following page contains interesting information on the relation of 7HVP with [HIV-1 Protease]. Full crystallographic information is available from OCA.
Reference
X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor., Swain AL, Miller MM, Green J, Rich DH, Schneider J, Kent SB, Wlodawer A, Proc Natl Acad Sci U S A. 1990 Nov;87(22):8805-9. PMID:2247451
Page seeded by OCA on Thu Feb 21 19:17:09 2008
