Rational engineering of activity and specificity in a serine protease
Rational engineering of activity and specificity in a serine protease
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DOI：
10.1038/nbt0297-146
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发表时间：
1997-02-01
影响因子：
46.9
通讯作者：
DiCera, E
中科院分区：
文献类型：
--
作者：
Dang, QD;Guinto, ER;DiCera, E
The discovery of the Na+-dependent allosteric regulation in serine proteases makes it possible to control catalytic activity and specificity in this class of enzymes in a way never considered before. We demonstrate that rational site-directed mutagenesis of residues controlling Na+ binding can profoundly alter the properties of a serine protease. By suppressing Na+ binding to thrombin, we shift the balance between procoagulant and anticoagulant activities of the enzyme. Those mutants, compared to wild-type, have reduced specificity toward fibrinogen, but enhanced or slightly reduced specificity toward protein C. Because this engineering strategy targets a fundamental regulatory mechanism, it is amenable of extension to other enzymes of biological and pharmacological importance.
