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

Jason Z. Niehaus; Mark T. Miedel; Misty Good; Allyson N. Wyatt; Stephen C. Pak; Gary A. Silverman; Cliff J. Luke

doi:10.1021/acs.biochem.5b01042

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

Jason Z. Niehaus, Mark T. Miedel, Misty Good, Allyson N. Wyatt, Stephen C. Pak, Gary A. Silverman, Cliff J. Luke

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	6756-6759
Number of pages	4
Journal	Biochemistry
Volume	54
Issue number	45
DOIs	https://doi.org/10.1021/acs.biochem.5b01042
State	Published - Oct 26 2015

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title = "SERPINB12 Is a Slow-Binding Inhibitor of Granzyme A and Hepsin",

abstract = "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.",

author = "Niehaus, {Jason Z.} and Miedel, {Mark T.} and Misty Good and Wyatt, {Allyson N.} and Pak, {Stephen C.} and Silverman, {Gary A.} and Luke, {Cliff J.}",

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AU - Niehaus, Jason Z.

AU - Miedel, Mark T.

AU - Good, Misty

AU - Wyatt, Allyson N.

AU - Pak, Stephen C.

AU - Silverman, Gary A.

AU - Luke, Cliff J.

PY - 2015/10/26

Y1 - 2015/10/26

N2 - 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.

AB - 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.

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JO - Biochemistry

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

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