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Characterization and comparative 3D modeling of CmPI-II, a novel ‘non-classical’ Kazal-type inhibitor from the marine snail Cenchritis muricatus (Mollusca).

Authors :
González, Yamile
Pons, Tirso
Gil, Jeovanis
Besada, Vladimir
Alonso-del-Rivero, Maday
Tanaka, Aparecida
Araujo, Mariana S.
Chávez, María A.
Source :
Biological Chemistry. Nov2007, Vol. 388 Issue 11, p1183-1194. 12p. 2 Diagrams, 1 Chart, 4 Graphs.
Publication Year :
2007

Abstract

The complete amino acid sequence obtained by electrospray ionization tandem mass spectrometry of the proteinase inhibitor CmPI-II isolated from Cenchritis muricatus is described. CmPI-II is a 5480-Da protein with three disulfide bridges that inhibits human neutrophil elastase (HNE) ( Ki 2.6±0.2 nM), trypsin ( Ki 1.1±0.9 nM), and other serine proteinases such as subtilisin A ( Ki 30.8±1.2 nM) and pancreatic elastase ( Ki 145.0±4.4 nM); chymotrypsin, pancreatic and plasma kallikreins, thrombin and papain are not inhibited. CmPI-II shares homology with the Kazal-type domain and may define a new group of ‘non-classical’ Kazal inhibitors according to its CysI-CysV disulfide bridge position. The 3D model of CmPI-II exhibits similar secondary structure characteristics to Kazal-type inhibitors and concurs with circular dichroism experiments. A 3D model of the CmPI-II/HNE complex provides a structural framework for the interpretation of its experimentally determined Ki value. The model shows both similar and different contacts at the primary binding sites in comparison with the structure of turkey ovomucoid third domain (OMTKY3)/HNE used as template. Additional contacts calculated at the protease-inhibitor interface could also contribute to the association energy of the complex. This inhibitor represents an exception in terms of specificity owing to its ability to strongly inhibit elastases and trypsin. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14316730
Volume :
388
Issue :
11
Database :
Academic Search Index
Journal :
Biological Chemistry
Publication Type :
Academic Journal
Accession number :
27329435
Full Text :
https://doi.org/10.1515/BC.2007.129