Počet záznamů: 1
Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin
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SYSNO ASEP 0557418 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin Tvůrce(i) Nikitin, D. (CZ)
Mican, J. (CZ)
Toul, J. (CZ)
Bednar, D. (CZ)
Pešková, Michaela (BFU-R)
Kittová, Patrícia (BFU-R)
Thalerová, Sandra (BFU-R)
Víteček, Jan (BFU-R) RID, ORCID
Damborský, J. (CZ)
Mikulik, R. (CZ)
Fleishman, S. (IL)
Prokop, Z. (CZ)
Marek, M. (CZ)Celkový počet autorů 13 Zdroj.dok. Computational and Structural Biotechnology Journal. - : Elsevier - ISSN 2001-0370
Roč. 20, MAR 2022 (2022), s. 1366-1377Poč.str. 12 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. SE - Švédsko Klíč. slova angiographic patency trial ; recombinant staphylokinase ; mechanical stability ; ischemic-stroke ; activator ; fibrin Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora BFU-R - RVO:68081707 UT WOS 000791774200010 EID SCOPUS 85126623274 DOI 10.1016/j.csbj.2022.03.004 Anotace Cardio-and cerebrovascular diseases are leading causes of death and disability, resulting in one of the highest socio-economic burdens of any disease type. The discovery of bacterial and human plasminogen activators and their use as thrombolytic drugs have revolutionized treatment of these pathologies. Fibrin specific agents have an advantage over non-specific factors because of lower rates of deleterious side effects. Specifically, staphylokinase (SAK) is a pharmacologically attractive indirect plasminogen activator protein of bacterial origin that forms stoichiometric noncovalent complexes with plasmin, promoting the conversion of plasminogen into plasmin. Here we report a computer-assisted re-design of the molecular surface of SAK to increase its affinity for plasmin. A set of computationally designed SAK mutants was produced recombinantly and biochemically characterized. Screening revealed a pharmacologically interesting SAK mutant with-7-fold enhanced affinity toward plasmin,-10-fold improved plasmin selectivity and moderately higher plasmin-generating efficiency in vitro. Collectively, the results obtained provide a framework for SAK engineering using computational affinity-design that could pave the way to next-generation of effective, highly selective, and less toxic thrombolytics.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2023 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S2001037022000794?via%3Dihub
Počet záznamů: 1