8hvp: Difference between revisions
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|PDB= 8hvp |SIZE=350|CAPTION= <scene name='initialview01'>8hvp</scene>, resolution 2.5Å | |PDB= 8hvp |SIZE=350|CAPTION= <scene name='initialview01'>8hvp</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=LOV:5-AMINO-4-HYDROXY-2-ISOPROPYL-7-METHYL-OCTANOIC+ACID'>LOV</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=8hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hvp OCA], [http://www.ebi.ac.uk/pdbsum/8hvp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=8hvp RCSB]</span> | |||
}} | }} | ||
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[[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 Mon Mar 31 05:45:15 2008'' | ||
Revision as of 05:45, 31 March 2008
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| , resolution 2.5Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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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