Exosite-driven substrate specificity and function in coagulation

Exosite determinants of serpin specificity.

Serpins form an enormous superfamily of 40-60-kDa proteins found in almost all types of organisms, including humans. Most are one-use suicide substrate serine and cysteine proteinase inhibitors that have evolved to finely regulate complex proteolytic pathways, such as blood coagulation, fibrinolysis, and inflammation. Despite distinct functions for each serpin, there is much redundancy in the p...

Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate

ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor d...

Dabigatran and Argatroban Diametrically Modulate Thrombin Exosite Function

Thrombin is a highly plastic molecule whose activity and specificity are regulated by exosites 1 and 2, positively-charged domains that flank the active site. Exosite binding by substrates and cofactors regulates thrombin activity by localizing thrombin, guiding substrates, and by inducing allosteric changes at the active site. Although inter-exosite and exosite-to-active-site allostery have be...

compactifications and function spaces on weighted semigruops

chapter one is devoted to a moderate discussion on preliminaries, according to our requirements. chapter two which is based on our work in (24) is devoted introducting weighted semigroups (s, w), and studying some famous function spaces on them, especially the relations between go (s, w) and other function speces are invesigated. in fact this chapter is a complement to (32). one of the main fea...

Substrate Specificity of MMPs