SERPINB12 Is a Slow-Binding Inhibitor of Granzyme A and Hepsin.
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.
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Jason Z
JZ
Niehaus
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Mark T
MT
Miedel
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Misty
M
Good
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Allyson N
AN
Wyatt
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Stephen C
SC
Pak
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Gary A
GA
Silverman
Department of Pediatrics and ‡Cell Biology and Physiology, University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh of UPMC , 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, United States.
Cliff J
CJ
Luke
D053804:Granzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D025941:Protein Interaction Mapping; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000187:drug effects*; D015843:Serpins / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; C445320:SERPINB12 protein, human; D015843:Serpins; D053804:Granzymes; D012697:Serine Endopeptidases; C055645:hepsin; C509212:GZMA protein, human