Structural findings and molecular modeling approach of a TFPI-like inhibitor

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. © 2014 bentham science publishers.