| Competitive parabolic inhibition of bovine trypsin by bis-benzamidines. | |
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MedLine Citation:
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PMID: 1342833 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Competitive parabolic inhibition, a rare type of inhibition of one-substrate enzymes, is described for alpha- and beta-trypsin. The enzymes were so inhibited by two bis-benzamidines, 4-4'-diazoamino-bis-benzamidine, Berenil (DABB) and its platinum complex, DABB-PtCl2, acting on acyl-amino acid and -peptidyl nitroanilides (Nan) substrates, when inhibitor concentrations exceed 10 mM and approach the millimolar range. 2. The type of nonlinear inhibition observed requires ternary complex formation between one enzyme molecule and two inhibitor molecules (M.E.M), and also permits the formation of the mixed ternary complex (M.E.S). Binding of the first DABB molecule to the active center of trypsin takes place with Ki values of ca. 1.50 microM for both alpha- and beta-trypsin. The secondary binding site binds the inhibitor with dissociation constants Ki2 close to 0.25 mM for both forms of the enzyme, as determined with different substrates. 3. The dissociation constants of the ternary mixed complexes (Ksi and Kis), however, depend on the structural features of the substrates, which are of negligible importance for Bz-Arg-Nan, but significant for Ac-Phe-Arg-Nan and D-Val-Leu-Arg-Nan, reflecting subsite interactions between S1-S3 and S'2. 4. Pentamidine, a diamidino-4,4'-diphenoxy-alkane with a flexible chain, behaved as a strict competitive inhibitor. This implies that the triazene moiety of DABB is involved in the interaction between the inhibitor and the secondary binding site of the enzyme. |
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Authors:
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R G Junqueira; E Silva; M Mares-Guia |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.] Volume: 25 ISSN: 0100-879X ISO Abbreviation: Braz. J. Med. Biol. Res. Publication Date: 1992 |
Date Detail:
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Created Date: 1994-02-18 Completed Date: 1994-02-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8112917 Medline TA: Braz J Med Biol Res Country: BRAZIL |
Other Details:
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Languages: eng Pagination: 873-87 Citation Subset: IM |
Affiliation:
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Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cattle Diminazene / analogs & derivatives*, pharmacology* Kinetics Organoplatinum Compounds / pharmacology Pentamidine / pharmacology Structure-Activity Relationship Substrate Specificity Trypsin / metabolism* Trypsin Inhibitors / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Organoplatinum Compounds; 0/Trypsin Inhibitors; 100-33-4/Pentamidine; 536-71-0/Diminazene; 90738-18-4/dichloro(4,4'-(diazoamino)bis(benzamidine))platinum complex; 908-54-3/diminazene aceturate; EC 3.4.21.4/Trypsin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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