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

Miscellaneous · Sun Jan 01 00:00:00 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
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

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