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Interaction of sea anemone Heteractis crispa Kunitz type polypeptides with pain vanilloid receptor TRPV1: In silico investigation.
- Source :
- Russian Journal of Bioorganic Chemistry; Mar2012, Vol. 38 Issue 2, p159-170, 12p
- Publication Year :
- 2012
-
Abstract
- Using methods of molecular biology we defined the structures of the 31 sea anemone Heteractis crispa genes encoding polypeptides which are structurally homologous to the Kunitz protease inhibitor family. The identified sequences have single-point amino acid substitutions, a high degree of homology with sequences of known Kunitz family members from H. crispa, and represent a combinatorial library of polypeptides. We generated their three-dimensional structures by methods of homology modeling. Analysis of their molecular electrostatic potential allowed the division of the polypeptides into three clusters. One of them includes polypeptides APHC1, APHC2, and APHC3 which have been shown to possess, in addition to their trypsin inhibitory activity, a unique property of inhibiting the pain vanilloid receptor TRPV1 in vitro and providing the analgesic effects in vivo. The spatial structure of the polypeptide complexes with TRPV1, the nature of the interactions, as well as functionally important structural elements involved in the complex formation, were established by molecular docking technique. The designed models allowed us to propose a hypothesis contributing to the understanding of how APHC1-APHC3 affect the pain signals transduction by TRPV1: apparently, relaxation time of the receptor increases due to binding of its two chains with a polypeptide molecule which disrupts functioning of TRPV1 and leads to partial inhibition of the signal transduction in electrophysiological experiments. [ABSTRACT FROM AUTHOR]
- Subjects :
- SEA anemones
POLYPEPTIDES
MOLECULAR biology
KUNITZ inhibitors
BIOCHEMISTRY
Subjects
Details
- Language :
- English
- ISSN :
- 10681620
- Volume :
- 38
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Russian Journal of Bioorganic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 73823786
- Full Text :
- https://doi.org/10.1134/S106816201202015X