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| | {{STRUCTURE_1hos| PDB=1hos | SCENE= }} | | {{STRUCTURE_1hos| PDB=1hos | SCENE= }} |
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| - | '''INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS'''
| + | ===INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS=== |
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| - | ==Overview==
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| - | 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) | + | The line below this paragraph, {{ABSTRACT_PUBMED_8347601}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8347601 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8347601}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Abdel-Meguid, S.]] | | [[Category: Abdel-Meguid, S.]] |
| | [[Category: Zhao, B.]] | | [[Category: Zhao, B.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:04:25 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:28:50 2008'' |
Revision as of 05:28, 1 July 2008
Template:STRUCTURE 1hos
INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE BY A C2-SYMMETRIC PHOSPHINATE SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS
Template:ABSTRACT PUBMED 8347601
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
Page seeded by OCA on Tue Jul 1 08:28:50 2008
