8hvp: Difference between revisions

Revision as of 22:49, 4 May 2008

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 Page seeded by OCA on Sun May 4 22:49:34 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:8hvp.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 8hvp |SIZE=350|CAPTION= <scene name='initialview01'>8hvp</scene>, resolution 2.5&Aring;
+The line below this paragraph, containing "STRUCTURE_8hvp", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|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>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_8hvp|  PDB=8hvp  |  SCENE=  }}
-|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>
-}}
 '''STRUCTURE AT 2.5-ANGSTROMS RESOLUTION OF CHEMICALLY SYNTHESIZED HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE COMPLEXED WITH A HYDROXYETHYLENE*-BASED INHIBITOR'''
@@ Line 34: / Line 31: @@
 [[Category: Tomasselli, A G.]]
 [[Category: Wlodawer, A.]]
-[[Category: hydrolase(acid proteinase)]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 22:49:34 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:45:15 2008''