1hos: Difference between revisions
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|PDB= 1hos |SIZE=350|CAPTION= <scene name='initialview01'>1hos</scene>, resolution 2.3Å | |PDB= 1hos |SIZE=350|CAPTION= <scene name='initialview01'>1hos</scene>, resolution 2.3Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=PHP:(2-PHENYL-1-CARBOBENZYL-OXYVALYL-AMINO)-ETHYL-PHOSPHINIC ACID'>PHP</scene> | |LIGAND= <scene name='pdbligand=PHP:(2-PHENYL-1-CARBOBENZYL-OXYVALYL-AMINO)-ETHYL-PHOSPHINIC+ACID'>PHP</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hos OCA], [http://www.ebi.ac.uk/pdbsum/1hos PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hos RCSB]</span> | |||
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[[Category: Abdel-Meguid, S.]] | [[Category: Abdel-Meguid, S.]] | ||
[[Category: Zhao, B.]] | [[Category: Zhao, B.]] | ||
[[Category: hydrolase(acid proteinase)]] | [[Category: hydrolase(acid proteinase)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:08:26 2008'' | ||
Revision as of 21:08, 30 March 2008
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| , resolution 2.3Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS
OverviewOverview
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 StructureAbout this Structure
1HOS is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
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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