Title: Atypical reactive center Kunitz-type inhibitor from the sea anemone Heteractis crispa
Authors: Gladkikh, Irina ×
Monastyrnaya, Margarita
Leychenko, Elena
Zelepuga, Elena
Chausova, Victoria
Isaeva, Marina
Anastyuk, Stanislav
Andreev, Yaroslav
Peigneur, Steve
Tytgat, Jan
Kozlovkaya, Emma #
Issue Date: Jul-2012
Publisher: Molecular Diversity Preservation International
Series Title: Marine Drugs vol:10 issue:7 pages:1545-65
Article number: 10.3390/md10071545
Abstract: The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high sequence identity (up to 98%) with the other known Kunitz-type sea anemones sequences. It was determined that the P1 Thr at the reactive site resulted in a decrease of the K(i) of InhVJ to trypsin and α-chymotrypsin (7.38 × 10(-8) M and 9.93 × 10(-7) M, respectively). By structure modeling the functional importance of amino acids at the reactive site as well as at the weak contact site were determined. The significant role of Glu45 for the orientation and stabilization of the InhVJ-trypsin complex was elucidated. We can suggest that there has been an adaptive evolution of the P1 residue at the inhibitor reactive site providing specialization or functional diversification of the paralogs. The appearance of a key so-called P1 Thr residue instead of Lys might lead to refinement of inhibitor specificity in the direction of subfamilies of serine proteases. The absence of Kv channel and TRPV1-receptor modulation activity was confirmed by electrophysiological screening tests.
ISSN: 1660-3397
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
× corresponding author
# (joint) last author

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