Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00557418" target="_blank" >RIV/68081707:_____/22:00557418 - isvavai.cz</a>

Alternative codes found

RIV/00159816:_____/22:00077750 RIV/00216224:14310/22:00126020

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2001037022000794?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2001037022000794?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.csbj.2022.03.004" target="_blank" >10.1016/j.csbj.2022.03.004</a>

Result language

angličtina

Original language name

Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin

Original language description

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/).

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Computational and Structural Biotechnology Journal

ISSN

2001-0370

e-ISSN

2001-0370

Volume of the periodical

20

Issue of the periodical within the volume

MAR 2022

Country of publishing house

SE - SWEDEN

Number of pages

12

Pages from-to

1366-1377

UT code for WoS article

000791774200010

EID of the result in the Scopus database

2-s2.0-85126623274