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Protein & Peptide Letters


ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Structural Findings and Molecular Modeling Approach of a TFPI-Like Inhibitor

Author(s): Kerly Fernanda Mesquita Pasqualoto, Andrea Balan, Sandra Alves Barreto, Simone Michaela Simons and Ana Marisa Chudzinski-Tavassi

Volume 21 , Issue 5 , 2014

Page: [452 - 457] Pages: 6

DOI: 10.2174/0929866520666131210115334

Price: $65


Specific blood coagulation inhibitors from hematophagous organisms, with different structures and novel mechanism of action, have been described and they represent promising agents for the treatment of a variety of human diseases related to coagulation and cancer. In our lab, the salivary glands transcriptome of the adult Amblyomma cajennense tick was previously characterized by expressed sequence tags (EST). A transcript that codes for a tissue factor pathway inhibitor (TFPI)-like protein with unique structure was found, and the recombinant form of this protein was named Amblyomin-X. This protein was able to inhibit the factor Xa amidolytic activity and the activation of factor X by the extrinsic tenase complex (FVIIa/TF). Herein, it was performed functional and structural evaluation of Amblyomin-X. The CD assay and molecular dynamics simulations revealed that Amblyomin-X is structurally stable and the naturally unfolded regions as well as the presence of three disulfide bridges in its Kunitz-type domain seem to sustain its inhibitory activity. Regarding the electrostatic potential mapping on the Kunitz-type region, the pattern of charged residues was not quite the same in comparison to human TFPI-1 and TFPI-2, pointing out there might be distinct functional and structural features, which are going to be experimentally exploited.

Keywords: Amblyomin-X, circular dichroism, molecular modeling, molecular dynamics simulation, TFPI-like inhibitor.

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