SERPINB12 Is a Slow-Binding Inhibitor of Granzyme A and Hepsin

被引:14
作者
Niehaus, Jason Z. [1 ]
Miedel, Mark T. [1 ]
Good, Misty [1 ]
Wyatt, Allyson N. [1 ]
Pak, Stephen C. [1 ]
Silverman, Gary A. [1 ,2 ,3 ]
Luke, Cliff J. [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15224 USA
[2] Univ Pittsburgh, Sch Med, Cell Biol & Physiol, Pittsburgh, PA 15224 USA
[3] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA
基金
美国国家卫生研究院;
关键词
HEPATOCYTE GROWTH-FACTOR; SERINE-PROTEASE HEPSIN; MEDIATED APOPTOSIS; PROSTATE-CANCER; CELLS; SUBSTRATE; SURFACE; IDENTIFICATION; PROTEOLYSIS; EXPRESSION;
D O I
10.1021/acs.biochem.5b01042
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The clade B/intracellular serpins protect cells from peptidase-mediated injury by forming covalent complexes with their targets. SERPINB12 is expressed in most tissues, especially at cellular interfaces with the external environment. This wide tissue distribution pattern is similar to that of granzyme A (GZMA). Because SERPINB12 inhibits trypsin-like serine peptidases, we determined whether it might also neutralize GZMA. SERPINB12 formed a covalent complex with GZMA and inhibited the enzyme with typical serpin slow-binding kinetics. SERPINB12 also inhibited Hepsin. SERPINB12 may function as an endogenous inhibitor of these peptidases.
引用
收藏
页码:6756 / 6759
页数:4
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