Investigation of the Active-Center of Rat Pancreatic Elastase

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Μικρογραφία εικόνας

Ημερομηνία

Συγγραφείς

Bieth, J. G.
Dirrig, S.
Jung, M. L.
Boudier, C.
Papamichael, E.
Sakarellos, C.
Dimicoli, J. L.

Τίτλος Εφημερίδας

Περιοδικό ISSN

Τίτλος τόμου

Εκδότης

Elsevier

Περίληψη

Τύπος

Είδος δημοσίευσης σε συνέδριο

Είδος περιοδικού

peer reviewed

Είδος εκπαιδευτικού υλικού

Όνομα συνεδρίου

Όνομα περιοδικού

Biochim Biophys Acta

Όνομα βιβλίου

Σειρά βιβλίου

Έκδοση βιβλίου

Συμπληρωματικός/δευτερεύων τίτλος

Περιγραφή

We have isolated rat pancreatic elastase I (EC 3.4.21.36) using a fast two-step procedure and we have investigated its active center with p-nitroanilide substrates and trifluoroacetylated inhibitors. These ligands were also used to probe porcine pancreatic elastase I whose amino acid sequence is 84% homologous to rat pancreatic elastase I as reported by MacDonald, et al. (Biochemistry 21, (1982) 1453-1463). Both proteinases exhibited non-Michaelian kinetics for substrates composed of three or four residues: substrate inhibition was observed for most enzyme substrate pairs, but with Ala3-p-nitroanilide, rat elastase showed substrate inhibition, whereas porcine elastase exhibited substrate activation. With most of the longer substrates, Michaelian kinetics were observed. The kcat/Km ratio was used to compare the catalytic efficiency of the two elastases on the different substrates. For both elastases, occupancy of subsite S4 was a prerequisite for efficient catalysis, occupancy of subsite S5 further increased the catalytic efficiency, P2 proline favored catalysis and P1 valine had an unfavorable effect. Rat elastase has probably one more subsite (S6) than its porcine counterpart. The rate-limiting step for the hydrolysis of N-succinyl-Ala3-p-nitroanilide by rat elastase was essentially acylation, whereas both acylation and deacylation rate constants participated in the turnover of this substrate by porcine elastase. For both enzymes, trifluoroacetylated peptides were much better inhibitors than acetylated peptides and trifluoroacetyldipeptide anilides were more potent than trifluoroacetyltripeptide anilides. A number of quantitative differences were found, however, and with one exception, trifluoroacetylated inhibitors were less efficient with rat elastase than with the porcine enzyme.

Περιγραφή

Λέξεις-κλειδιά

Pancreatic elastase, Elastase substrate, Elastase inhibitor, Substrate activation, Substrate inhibition, (Rat), (Pig)

Θεματική κατηγορία

Παραπομπή

Σύνδεσμος

<Go to ISI>://A1989R836200010

Γλώσσα

en

Εκδίδον τμήμα/τομέας

Όνομα επιβλέποντος

Εξεταστική επιτροπή

Γενική Περιγραφή / Σχόλια

Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος

Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας

Πίνακας περιεχομένων

Χορηγός

Βιβλιογραφική αναφορά

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