Isolation and serine protease inhibitory activity of the 44-residue, C-terminal fragment of alpha 1-antitrypsin from human placenta.
alpha 1-Antitrypsin (AAT) is a potent fluid-phase inhibitor of serine proteases. It forms a tightly bound, stoichiometric complex with these enzymes and is inactivated by cleavage within its reactive center. Evidence is here presented, that the 44-residue C-terminal fragment of AAT, termed SPAAT (short peptide from AAT), is found in human tissue, where it is apparently bound to the extracellular matrix (ECM). The identity of SPAAT was established by amino acid sequence analysis through its 40 N-terminal residues. Placental SPAAT inhibits chymotrypsin, human neutrophil elastase (HNE) and pancreatic elastase, but has no effect on trypsin. Unlike AAT, both placental and chemically-synthesized SPAAT are reversible, competitive inhibitors of chymotrypsin with Kl's of 0.92 and 7.5 microM, respectively. Both AAT and placental SPAAT also bind to diisopropyl fluorophosphate (DFP)-treated HNE as well as cathepsin G. SPAAT may therefore play an important role in the protection of ECM proteins, such as elastin, proteoglycans (PG) and/or collagen, from inappropriate attack by serine proteases.
Niemann
M A
MA
Department of Biochemistry, University of Alabama, Birmingham 35294.
Narkates
A J
AJ
Miller
E J
EJ
D000595:Amino Acid Sequence; D005109:Extracellular Matrix / Q000201:enzymology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000302:isolation & purification / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D000515:alpha 1-Antitrypsin; D012697:Serine Endopeptidases