Human alpha-thrombin inhibition by the active site titrant N-alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: A comparative kinetic and X-ray crystallographic study (Articolo in rivista)

Type
Label
  • Human alpha-thrombin inhibition by the active site titrant N-alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: A comparative kinetic and X-ray crystallographic study (Articolo in rivista) (literal)
Anno
  • 1996-01-01T00:00:00+01:00 (literal)
Alternative label
  • Nardini, M.; Pesce, A.; Rizzi, M.; Casale, E.; Ferraccioli, R; Balliano, G.; Milla, P.; Ascenzi, P.; Bolognesi, M.(1) (1996)
    Human alpha-thrombin inhibition by the active site titrant N-alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: A comparative kinetic and X-ray crystallographic study
    in Journal of Molecular Biology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Nardini, M.; Pesce, A.; Rizzi, M.; Casale, E.; Ferraccioli, R; Balliano, G.; Milla, P.; Ascenzi, P.; Bolognesi, M.(1) (literal)
Pagina inizio
  • 851 (literal)
Pagina fine
  • 859 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 258 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • [ 1 ] UNIV GENOA,CTR BIOTECNOL AVANZATE IST,I-16126 GENOA,ITALY [ 2 ] UNIV GENOA,DIPARTIMENTO FIS,I-16126 GENOA,ITALY [ 3 ] UNIV PAVIA,DIPARTIMENTO GENET & MICROBIOL A BUZZATI TRAV,I-27100 PAVIA,ITALY [ 4 ] PHARMACIA CTR RIC,I-20014 NERVIANO,MI,ITALY [ 5 ] UNIV TURIN,DIPARTIMENTO SCI & TECNOL FARMACO,I-10125 TURIN,ITALY [ 6 ] TERZA UNIV ROMA,DIPARTIMENTO BIOL,I-00154 ROME,ITALY (literal)
Titolo
  • Human alpha-thrombin inhibition by the active site titrant N-alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: A comparative kinetic and X-ray crystallographic study (literal)
Abstract
  • Kinetics for the hydrolysis of the chromogenic active site titrant N-alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp) catalyzed by bovine beta-trypsin, bovine alpha-thrombin, human alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, the M(r) 33,000 and M(r) 54,000 species of human urokinase, as well as by porcine pancreatic beta-kallikrein-A and B have been obtained between pH 6.0 and 8.0, at 21.0 degrees C. Moreover, the three dimensional structure of the human alpha-thrombin-(hirugen). Dmc-azaLys acyl . enzyme complex has been analyzed and refined by X-ray crystallography at 2.0 Angstrom resolution (R-factor = 0.168). As observed for bovine beta-trypsin, the acylating inhibitor molecule is covalently bound to the Ser195 catalytic residue, filling the human alpha-thrombin S-1 primary specificity subsite with its lysyl side-group. However, the carbonyl group of the scissile human alpha-thrombin . Dmc-azalys acyl bond does not occupy properly the oxyanion binding hole. At variance from the bovine beta-trypsin . Dmc-azaLys acyl . enzyme structure, a second, not covalently bound, inhibitor molecule, partly shielded by the 60-insertion loop of human alpha-thrombin, is contacting the enzyme ''aryl-binding site''. (literal)
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