The bovine basic pancreatic trypsin inhibitor (Kunitz inhibitor): a milestone protein.
The pancreatic Kunitz inhibitor, also known as aprotinin, bovine basic pancreatic trypsin inhibitor (BPTI), and trypsin-kallikrein inhibitor, is one of the most extensively studied globular proteins. It has proved to be a particularly attractive and powerful tool for studying protein conformation as well as molecular bases of protein/protein interaction(s) and (macro)molecular recognition. BPTI has a relatively broad specificity, inhibiting trypsin- as well as chymotrypsin- and elastase-like serine (pro)enzymes endowed with very different primary specificity. BPTI reacts rapidly with serine proteases to form stable complexes, but the enzyme: inhibitor complex formation may involve several intermediates corresponding to discrete reaction steps. Moreover, BPTI inhibits the nitric oxide synthase type-I and -II action and impairs K+ transport by Ca2+-activated K+ channels. Clinically, the use of BPTI in selected surgical interventions, such as cardiopulmonary surgery and orthotopic liver transplantation, is advised, as it significantly reduces hemorrhagic complications and thus blood-transfusion requirements. Here, the structural, inhibition, and bio-medical aspects of BPTI are reported.
Ascenzi
Paolo
P
Dipartimento di Biologia, Università Roma Tre, Italy. ascenzi@uniroma3.it
Bocedi
Alessio
A
Bolognesi
Martino
M
Spallarossa
Andrea
A
Coletta
Massimo
M
De Cristofaro
Raimondo
R
Menegatti
Enea
E
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D007700:Kinetics; D008958:Models, Molecular; D010195:Pancreatitis / Q000188:drug therapy; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D013816:Thermodynamics; D014361:Trypsin Inhibitors / Q000378:metabolism
D014361:Trypsin Inhibitors; D007611:Aprotinin; D012697:Serine Endopeptidases; D002918:Chymotrypsin