1rgq
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1rgq |SIZE=350|CAPTION= <scene name='initialview01'>1rgq</scene>, resolution 2.90Å | |PDB= 1rgq |SIZE=350|CAPTION= <scene name='initialview01'>1rgq</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=AKP:N-(PYRAZIN-2-YLCARBONYL)LEUCYLISOLEUCYL-N~1~-{1-[2-({1-CARBOXY-2-[4-(PHOSPHONOOXY)PHENYL]ETHYL}AMINO)-1,1-DIHYDROXY-2-OXOETHYL]BUT-3-ENYL}-3-CYCLOHEXYLALANINAMIDE'>AKP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Hepacivirin Hepacivirin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.98 3.4.21.98] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hepacivirin Hepacivirin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.98 3.4.21.98] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgq OCA], [http://www.ebi.ac.uk/pdbsum/1rgq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rgq RCSB]</span> | ||
}} | }} | ||
| Line 31: | Line 34: | ||
[[Category: Saldivar, A.]] | [[Category: Saldivar, A.]] | ||
[[Category: Stoll, V S.]] | [[Category: Stoll, V S.]] | ||
| - | [[Category: AKP]] | ||
| - | [[Category: ZN]] | ||
[[Category: hepatitis c virus protease keto amide peptide inhibitor]] | [[Category: hepatitis c virus protease keto amide peptide inhibitor]] | ||
| - | ''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 23:27:56 2008'' |
Revision as of 20:27, 30 March 2008
| |||||||
| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Hepacivirin, with EC number 3.4.21.98 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
M9A HCV Protease complex with pentapeptide keto-amide inhibitor
Overview
A series of novel peptidyl-alpha-ketoamide compounds were evaluated as inhibitors of the deltaNS3-NS4A serine protease from the hepatitis C virus. These peptidyl-alpha-ketoamide inhibitors with Ki values ranging from 0.17 nM to 5.6 microM exhibited slow-binding inhibition. Kinetic studies established one-step kinetic mechanisms and dissociation rate constants in the 3-7 x 10(-5) s(-1) range for these compounds. The association rate constants, which ranged from 10 to 263,000 M(-1) s(-1), were responsible for the greater than four order of magnitude overall binding affinity range exhibited by this series. An X-ray crystal structure of a protease-inhibitor complex revealed an unusual interaction between the oxyanion of the adduct and the protein as well as a significant movement in the S1' region of the protein loop comprising residues 35-42. These results are quite different from peptidyl-alpha-ketoacid inhibition of HCV protease, which reportedly undergoes no notable conformational changes and proceeds with a two-step slow-binding kinetic mechanism.
About this Structure
1RGQ is a Protein complex structure of sequences from Hepatitis c virus. Full crystallographic information is available from OCA.
Reference
Hepatitis C NS3 protease inhibition by peptidyl-alpha-ketoamide inhibitors: kinetic mechanism and structure., Liu Y, Stoll VS, Richardson PL, Saldivar A, Klaus JL, Molla A, Kohlbrenner W, Kati WM, Arch Biochem Biophys. 2004 Jan 15;421(2):207-16. PMID:14984200
Page seeded by OCA on Sun Mar 30 23:27:56 2008
