The S'-subsite specificity of endoproteinase Glu-C (V8 proteinase) was studied by acyl transfer reactions using Z-Glu-OMe as acyl donor and a series of amino acid- and peptide-derived nucleophiles. The partition constant, which characterizes specificity, was determined by a method based on the integrated rate equation. V8 proteinase prefers amino acid residues with hydrophobic side chains in the P'1 position. Di- and tripeptide amides are more efficient nucleophilic amino components than amino acid amides.
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http://dx.doi.org/10.1016/0304-4165(90)90042-u | DOI Listing |
Blood Adv
May 2017
Department of Biochemistry and Molecular Biology and.
The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important.
View Article and Find Full Text PDFJ Biomol Struct Dyn
December 2014
a Department of Microbiology , West Bengal State University, Barasat, Berunanpukuria, P.O. Malikapur, North 24 Parganas, Kolkata 700126 , West Bengal , India.
Meprins are complex and highly glycosylated multi-domain enzymes that require post-translational modifications to reach full activity. Meprins are metalloproteases of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR). Human meprin-α and -β protease subunits are 55% identical at the amino acid level, however the substrate and peptide bond specificities vary markedly.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2013
Center for Integrated Protein Science Munich, Lehrstuhl für Chemie der Biopolymere, Technische Universität München, 85354 Freising, Germany.
Rhomboid proteases are evolutionary conserved intramembrane serine proteases. Because of their emerging role in many important biological pathways, rhomboids are potential drug targets. Unfortunately, few chemical tools are available for their study.
View Article and Find Full Text PDFBioorg Med Chem
May 2009
Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
A series of mechanism-based inhibitors designed to interact with the S' subsites of serine proteases was synthesized and their inhibitory activity toward the closely-related serine proteases human neutrophil elastase (HNE) and proteinase 3 (PR 3) was investigated. The compounds were found to be time-dependent inhibitors of HNE and were devoid of any inhibitory activity toward PR 3. The results suggest that highly selective inhibitors of serine proteases whose primary substrate specificity and active sites are similar can be identified by exploiting differences in their S' subsites.
View Article and Find Full Text PDFBiochim Biophys Acta
November 2006
Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
A simulation methodology for predicting the time-course of enzymatic digestions is described. The model is based solely on the enzyme's subsite architecture and concomitant binding energies. This allows subsite binding energies to be used to predict the evolution of the relative amounts of different products during the digestion of arbitrary mixtures of oligomeric or polymeric substrates.
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