8hvp: Difference between revisions
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[[Image:8hvp.gif|left|200px]] | [[Image:8hvp.gif|left|200px]] | ||
'''STRUCTURE AT 2.5-ANGSTROMS RESOLUTION OF CHEMICALLY SYNTHESIZED HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE COMPLEXED WITH A HYDROXYETHYLENE*-BASED INHIBITOR''' | {{Structure | ||
|PDB= 8hvp |SIZE=350|CAPTION= <scene name='initialview01'>8hvp</scene>, resolution 2.5Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= | |||
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'''STRUCTURE AT 2.5-ANGSTROMS RESOLUTION OF CHEMICALLY SYNTHESIZED HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE COMPLEXED WITH A HYDROXYETHYLENE*-BASED INHIBITOR''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
8HVP is a [ | 8HVP 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=8HVP OCA]. | ||
==Reference== | ==Reference== | ||
Structure at 2.5-A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene-based inhibitor., Jaskolski M, Tomasselli AG, Sawyer TK, Staples DG, Heinrikson RL, Schneider J, Kent SB, Wlodawer A, Biochemistry. 1991 Feb 12;30(6):1600-9. PMID:[http:// | Structure at 2.5-A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene-based inhibitor., Jaskolski M, Tomasselli AG, Sawyer TK, Staples DG, Heinrikson RL, Schneider J, Kent SB, Wlodawer A, Biochemistry. 1991 Feb 12;30(6):1600-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1993177 1993177] | ||
[[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 19:15:30 2008'' | ||
Revision as of 20:15, 20 March 2008
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STRUCTURE AT 2.5-ANGSTROMS RESOLUTION OF CHEMICALLY SYNTHESIZED HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE COMPLEXED WITH A HYDROXYETHYLENE*-BASED INHIBITOR
OverviewOverview
The crystal structure of a complex between chemically synthesized human immunodeficiency virus type 1 (HIV-1) protease and an octapeptide inhibitor has been refined to an R factor of 0.138 at 2.5-A resolution. The substrate-based inhibitor, H-Val-Ser-Gln-Asn-Leu psi [CH(OH)CH2]Val-Ile-Val-OH (U-85548e) contains a hydroxyethylene isostere replacement at the scissile bond that is believed to mimic the tetrahedral transition state of the proteolytic reaction. This potent inhibitor has Ki less than 1 nM and was developed as an active-site titrant of the HIV-1 protease. The inhibitor binds in an extended conformation and is involved in beta-sheet interactions with the active-site floor and flaps of the enzyme, which form the substrate/inhibitor cavity. The inhibitor diastereomer has the S configuration at the chiral carbon atom of the hydroxyethylene insert, and the hydroxyl group is within H-bonding distance of the two active-site carboxyl groups in the enzyme dimer. The two subunits of the enzyme are related by a pseudodyad, which superposes them at a 178 degrees rotation. The main difference between the subunits is in the beta turns of the flaps, which have different conformations in the two monomers. The inhibitor has a clear preferred orientation in the active site and the alternative conformation, if any, is a minor one (occupancy of less than 30%). A new model of the enzymatic mechanism is proposed in which the proteolytic reaction is viewed as a one-step process during which the nucleophile (water molecule) and electrophile (an acidic proton) attack the scissile bond in a concerted manner.
About this StructureAbout this Structure
8HVP is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Structure at 2.5-A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene-based inhibitor., Jaskolski M, Tomasselli AG, Sawyer TK, Staples DG, Heinrikson RL, Schneider J, Kent SB, Wlodawer A, Biochemistry. 1991 Feb 12;30(6):1600-9. PMID:1993177
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