The Bowman-Birk inhibitor. Trypsin- and chymotrypsin-inhibitor from soybeans.
Four decades of studies on the isolation, characterization, properties, structure, function and possible uses of the Bowman-Birk trypsin- and chymotrypsin-inhibitor from soybeans are reviewed. Starting from Bowman's Acetone Insoluble factor, designated Ai, AA and SBTIAA, the Bowman-Birk inhibitor (BBI) was found to be a protein molecule consisting of a chain of 71 amino acids cross linked by 7 disulfide bonds, with a tendency to self-associate. BBI possesses two independent sites of inhibition, one at Lys 16-Ser 17 against trypsin and the other at Leu 43-Ser 44 against chymotrypsin. It forms a 1:1 complex with either trypsin or chymotrypsin and a ternary complex with both enzymes. Ingestion of BBI by rats, chicks or quails affects the size and protein biosynthesis of the pancreas. Establishment of the full covalent structure of BBI revealed a high homology in the sequences around the two inhibitory sites, suggesting evolutionary gene duplication from a single-headed ancestral inhibitor. Scission of BBI by CNBr followed by pepsin results in two active fragments, one that inhibits trypsin and the other, chymotrypsin. Replacements and substitutions in the reactive sites result in changes in inhibitory activity and in specificity of inhibition. Conformation studies, labeling of BBI with a photoreactive reagent, chemical synthesis of cyclic peptides that include inhibitory sites, in vitro synthesis of BBI, and species specificity regarding the inhibited enzymes are described. The significance of BBI as a prototype of a family of inhibitors present in all legume seeds is discussed.
D000096:Acetone; D000595:Amino Acid Sequence; D005075:Biological Evolution; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000302:isolation & purification; D010777:Photochemistry; D011487:Protein Conformation; D012995:Solubility; D013025:Glycine max / Q000032:analysis; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000302:isolation & purification*
D004791:Enzyme Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; D000096:Acetone; D002918:Chymotrypsin