1rgq
From Proteopedia
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| - | [[Image:1rgq.gif|left|200px]] | + | [[Image:1rgq.gif|left|200px]] |
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| - | '''M9A HCV Protease complex with pentapeptide keto-amide inhibitor''' | + | {{Structure |
| + | |PDB= 1rgq |SIZE=350|CAPTION= <scene name='initialview01'>1rgq</scene>, resolution 2.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <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> | ||
| + | |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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''M9A HCV Protease complex with pentapeptide keto-amide inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RGQ is a [ | + | 1RGQ is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGQ OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/14984200 14984200] |
[[Category: Hepacivirin]] | [[Category: Hepacivirin]] | ||
[[Category: Hepatitis c virus]] | [[Category: Hepatitis c virus]] | ||
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[[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 Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:51:26 2008'' |
Revision as of 11:51, 20 March 2008
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| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Hepacivirin, with EC number 3.4.21.98 | ||||||
| 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
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