1hos
From Proteopedia
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| - | [[Image:1hos.gif|left|200px]] | + | [[Image:1hos.gif|left|200px]] |
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| - | '''INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS''' | + | {{Structure |
| + | |PDB= 1hos |SIZE=350|CAPTION= <scene name='initialview01'>1hos</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PHP:(2-PHENYL-1-CARBOBENZYL-OXYVALYL-AMINO)-ETHYL-PHOSPHINIC ACID'>PHP</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HOS is a [ | + | 1HOS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HOS OCA]. |
==Reference== | ==Reference== | ||
| - | Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis., Abdel-Meguid SS, Zhao B, Murthy KH, Winborne E, Choi JK, DesJarlais RL, Minnich MD, Culp JS, Debouck C, Tomaszek TA Jr, et al., Biochemistry. 1993 Aug 10;32(31):7972-80. PMID:[http:// | + | Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis., Abdel-Meguid SS, Zhao B, Murthy KH, Winborne E, Choi JK, DesJarlais RL, Minnich MD, Culp JS, Debouck C, Tomaszek TA Jr, et al., Biochemistry. 1993 Aug 10;32(31):7972-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8347601 8347601] |
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hydrolase(acid proteinase)]] | [[Category: hydrolase(acid proteinase)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:39:42 2008'' |
Revision as of 09:39, 20 March 2008
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| , resolution 2.3Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS
Overview
The human immunodeficiency virus type 1 (HIV-1) protease is a potential target of acquired immune deficiency syndrome (AIDS) therapy. A highly potent, perfectly symmetrical phosphinate inhibitor of this enzyme, SB204144, has been synthesized. It is a competitive inhibitor of HIV-1 protease, with an apparent inhibition constant of 2.8 nM at pH 6.0. The three-dimensional structure of SB204144 bound to the enzyme has been determined at 2.3-A resolution by X-ray diffraction techniques and refined to a crystallographic discrepancy factor, R (= sigma parallel F(o) magnitude to - Fc parallel/sigma magnitude of F(o)), of 0.178. The inhibitor is held in the enzyme active site by a set of hydrophobic and hydrophilic interactions, including an interaction between Arg8 and the center of the terminal benzene rings of the inhibitor. The phosphinate establishes a novel interaction with the two catalytic aspartates; each oxygen of the central phosphinic acid moiety interacts with a single oxygen of one aspartic acid, establishing a very short (2.2-2.4 A) oxygen-oxygen contact. As with the structures of penicillopepsin bound to phosphinate and phosphonate inhibitors [Fraser, M. E., Strynadka, N. C., Bartlett, P. A., Hanson, J. E., & James, M. N. (1992) Biochemistry 31, 5201-14], we interpret this short distance and the stereochemical environment of each pair of oxygens in terms of a hydrogen bond that has a symmetric single-well potential energy curve with the proton located midway between the two atoms.(ABSTRACT TRUNCATED AT 250 WORDS)
About this Structure
1HOS is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis., Abdel-Meguid SS, Zhao B, Murthy KH, Winborne E, Choi JK, DesJarlais RL, Minnich MD, Culp JS, Debouck C, Tomaszek TA Jr, et al., Biochemistry. 1993 Aug 10;32(31):7972-80. PMID:8347601
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