On the structure, function and biosynthesis of human inter-. alpha. inhibitor

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:5674094

Swaim, M W

Human inter-{alpha} inhibitor (I{alpha}I) is a {approx}200-kD serum glycoprotein with serine proteinase-inhibitory activity whose physiologic role remains unclear. I{alpha}I is related to smaller inhibitors found in physiologic fluids and is a complex of {approx}40-kD light and {approx}90-kD heavy chains. I{alpha}I proteinase-inhibitory activity resides exclusively in the light chain, which has tandem Kunitz inhibitory domains with methionine and arginine residues, respectively, at position P{sub 1}. The inhibitory activity of the reactive centers was heretofore uncharacterized. Cis-dichlorodiammineplatinum (II) (cis-DDP) reacts with sulfur containing residues in a limited and selective fashion. In preliminary studies, cis-DDP was evaluated as a reagent to modify the methionine reactive centers of two other plasma proteinase inhibitors, {alpha}{sub 1}-antitrypsin and {alpha}{sub 2}-antiplasmin. Cis-DDP readily abolished the proteinase-inhibitory activity of both proteins. Methionine oxidation, papain digestion, and platinum binding assays showed that cis-DDP inactivates {alpha}-antitrypsin by binding exclusively to its reactive-center methionine. Cis-DDP partially eliminated I{alpha}I inhibitory activity against cathepsin G and neutrophil elastase but did not affect inhibition of trypsin or chymotrypsin. Conversely, reaction with the arginine-modifying reagent 2,3-butanedione afforded complete loss of activity against trypsin and chymotrypsin but partial loss of activity against cathepsin G and elastase. Employment of both reagents eliminated inhibition of cathepsin G and elastase. Thus eathepsin G and elastase are apparently inhibited at either reactive center. Trypsin and chymotrypsin are inhibited exclusively at the arginine reactive center.

• Research Organization: Duke Univ., Durham, NC (USA)
• OSTI ID: 5674094
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYME ACTIVITY
ENZYME INHIBITORS
EVEN-ODD NUCLEI
GLYCOPROTEINS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MAN
METHIONINE
MOLECULAR STRUCTURE
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
SULFUR 35
SULFUR ISOTOPES
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES