title: Novel chromaffin granule serpins, endopin 1 and endopin 2: endogenous protease inhibitors with distinct target protease specificities.
abstract: Endopin 1 and endopin 2 represent two novel serpin protease inhibitors localized within chromaffin granules, secretory vesicles of adrenomedullary chromaffin cells that represent a model neuroendocrine cell for synthesis and secretion of peptide neurotransmitters. This chapter describes the molecular features of the primary sequences of endopin 1 and endopin 2 that provided prediction of their distinct target protease specificities. Endopin 1 inhibits trypsin that cleaves at basic residues. In contrast, endopin 2 possesses cross-class inhibition of papain and elastase that represent cysteine and serine proteases, respectively. Cell biological studies indicate that endopin 1 and endopin 2 are localized within chromaffin granules. These results implicate endopin 1 inhibition in vivo of trypsin-like proteases in secretory vesicles, and endopin 2 inhibition of papain- or elastase-like proteases. Indeed, endopin 2 inhibits the endogenous cysteine protease PTP (prohormone thiol protease), present in chromaffin granules, that participates in the proteolytic processing of proenkephalin. These findings indicate the presence of endogenous endopin 1 and endopin 2 in secretory vesicle function.
authors.affiliation: Buck Institute for Age Research, Novato, California 94945, USA. vhook@buckinstitute.org
authors.forename: Vivian Y H
authors.initials: VY
authors.lastname: Hook
authors.forename: Sukkid
authors.initials: S
authors.lastname: Yasothornsrikul
authors.forename: Shin-Rong
authors.initials: SR
authors.lastname: Hwang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019439:Chromaffin Cells / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000378:metabolism* / Q000502:physiology*
chemical_list: D011994:Recombinant Proteins; C402207:SERPINA3 protein, Bos taurus; D015843:Serpins; C412321:endopin 2