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3.4.21.98: hepacivirin

This is an abbreviated version!
For detailed information about hepacivirin, go to the full flat file.

Word Map on EC 3.4.21.98

Reaction

Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1' =

Synonyms

Cpro-2, Cpro-2 proteinase, Den2 protease, HCV NS3, HCV NS3 protease, HCV NS3/4A, HCV NS3/4A protease, Hepacivirin, hepatitis C virus NS3 serine protease, hepatitis C virus NS3/4A protease, non-structural 3 protein, nonstructural 3 protease, nonstructural protein 3, nonstructural protein 3-4A serine protease, nonstructural protein 3-4Agene, nonstructural protein 3/4A protease, NS2/3 protease, NS2B-NS3 proteinase, NS2B/NS3 protease, NS3, NS3 protease, NS3 protein, NS3 proteinase, NS3 serine protease, NS3 serine proteinase, NS3-4A, NS3-4A protease, NS3-4A serine protease, NS3-4A serine protease complex, NS3-4A serine proteinase, NS3-NS4A protease, NS3-protease, NS3-SP, NS3/4a, NS3/4A protease, NS3/4A protease complex, NS3/4A serine protease, NS34Agene, NS3?4A, NS5A-5B protease, P70, polyprotein-processing proteinase NS3, proteinase NS3, proteinase, polyprotein-processing, NS3, sc-protease, serine protease NS3, serine proteinase NS3

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.98 hepacivirin

Crystallization

Crystallization on EC 3.4.21.98 - hepacivirin

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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
3D structural model threaded through a template crystal structure of HCV-1b NS3 protease. The model protease has rigid structural features. Local dynamics and 4D analysis of the interactions between the catalytic triad residues His57, Asp81, and Ser139 indicate conformational instability of the catalytic site in HCV-4a NS3 protease
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crystal structure of a recombinant truncated HCV NS3 protease domain complexed with a synthetic peptide encompassing the essential NS3-binding region of NS4A at 2.5 A resolution
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crystal structure of protease-inhibitor complex
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genotype 1a HCV protease domain with R155K mutation, in a complex with an NS4A co-factor peptide, at 2.5 A resolution. Crystals belong to space group R32 with unit cell dimensions of a=225.31 A, b=225.31 A, c=75.66 A, alpha=90°, beta=90°, and gamma=120°
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in complex with inhibitor (4R,6S,7Z,15S,17S)-17-[((8-chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl)oxy)methyl]-13-methyl-N-[(1-methylcyclopropyl)sulfonyl]-2,14-dioxo-1,3,13-triazatricyclo[13.2.0.0-4,6-]heptadec-7-ene-4-carboxamide, to 2.84 A resolution. Structure shows that the canonical hydrogen bonds between the amide moieties of the inhibitor and the NS3 protease main chain from which amino acids R155 and A157 are involved in hydrogen bond donor/acceptor interactions are maintained
in complex with inhibitor 3-cyclohexyl-2,5-dioxo-12-oxa-1,4-diazatricyclo(11.5.3.016,20)-henicosa-13(21),14,16(20)-triene-18-carboxylic acid ((((1-(dimethylcarbamoylphenylmethyl)carbamoyl)methyl)aminooxalyl)butyl)-amide
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in complex with inhibitor N-(tert-butylcarbamoyl)-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-[(7-methoxy-2-phenylquinolin-4-yl)oxy]-L-prolinamide. The compound is bound to the active site of HCV protease through an anti-parallel beta-sheet between the inhibitor backbone and the E2-strand of the protease
in complex with inhibitor tert-butyl (1-cyclohexyl-2-[(3R)-3-[(1-[[(2-[[(1S)-2-(dimethylamino)-2-oxo-1-phenylethyl]amino]-2-oxoethyl)amino](oxo)acetyl]pentyl)carbamoyl]-2-azabicyclo[2.2.1]hept-2-yl]-2-oxoethyl)carbamate
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modeling of enzyme active site with inhibitor N-[(2S)-2-(acetylamino)-2-cyclohexylacetyl]-L-valyl-(4R)-N-[(1S,2R)-1-carboxy-2-ethenylcyclopropyl]-4-[(2-phenylquinolin-4-yl)oxy]-L-prolinamide
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molecular dynamics simulations using inhibitors boceprevir, telaprevir, danoprevir, and BI201335. The key residues involved in inhibitor binding are residues 41-43, 57, 81, 136-139, 155-159, and 168 in the NS3 domain. The van der Waals interactions yield the main driving force for inhibitor binding at the protease active site for the cleavage reaction. In addition, the highest number of hydrogen bonds is formed at the reactive P1 site of the four studied inhibitors.The P3 site is most likely to be recognized by the A157 backbone. The relative binding affinities predicted for the four inhibitors are in a somewhat similar trend to their experimentally derived biological activities
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mutant V36M in a complex with NS4A cofactor peptide, at 2.4 A resolution
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NS3-4A is made of two domains both composed of a beta-barrel and two short alpha-helices with the catalytic triad located in a crevice formed at the interface between the two domains. NS3-4A protease in complex with inhibitors
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NS3/4A crystal structures of both host cell cleavage sites are determined and compared to the crystal structures of viral substrates. Two distinct protease conformations are observed and correlate with substrate specificity: 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes
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shallow featureless active site, highly solvent exposed
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sitting drop vapour diffusion method, crystal structure of the protease domain with a chymotrypsin-like fold, complexed with NS4 cofactor and with two potent, reversible covalent inhibitors spanning the P1-P4 residues,tert-butyloxacrybonyl-L-Glu-L-Leu-L-(difluoro)aminobutyric acid and benzyloxycarbonyl-L-Ile-L-Leu-L-(difluoro)aminobutyric acid
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structure NS3 protease domain complexed with a synthetic NS4A cofactor peptide
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crystal structure of NS2B-NS3pro cocrystallized with the tetrapeptide aldehyde Bz-nKRR-HS1. S2 pockets are the key peptide recognition sites. A residue capable of both pi-stacking and hydrogen bonding is favored in the S1 pocket, while a positively charged residue is preferred in the S2 pocket
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crystal structure of NS2B/NS3 protease reveals that Asn-84 of the NS2B cofactor is within hydrogen bonding distance of the P2 Lys of the bound ligand.Asn-84 is located within a highly conserved region of the cofactor, the Gly residue on the N-terminal side is completely conserved, and the third residue on the C-terminal side is a highly conserved hydrophobic Leu or Ile
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modeling of enzyme based on structures of dengue-2 and hepatitis C viral proteases
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