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

Dmitri Nikitin,Jan Mican,Martin Toul,David Bednar,Michaela Peskova,Patricia Kittova,Sandra Thalerova,Jan Vitecek,Jiri Damborsky,Robert Mikulik,Sarel J Fleishman,Zbynek Prokop,Martin Marek

Computational and Structural Biotechnology Journal（2022）

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摘要

•Computational re-design of staphylokinase (SAK) for enhanced affinity toward plasmin.•Designed SAK mutants are biochemically and structurally characterized.•A novel SAK mutant with substantially improved pharmacological properties is identified.•New avenues for effective, highly selective, and less toxic thrombolytics are highlighted.

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关键词

Acute myocardial infarction,Stroke treatments,Thrombolytics,Plasminogen activators,Staphylokinase,Rational design,Affinity engineering,Enzyme kinetics,AffiLib

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