Disease relevance of PTI

• The cDNA for bovine spleen trypsin inhibitor (SI), a homologue of bovine pancreatic trypsin inhibitor (BPTI), including the natural mammalian presequence was expressed in tobacco using Agrobacterium tumefaciens-mediated transformation [1].
• However, when expressed at 37 degrees C in E. coli, or when refolded at 37 degrees or 52 degrees C in vitro, the mutant proteins folded readily into the native conformation, albeit at a rate somewhat slower than that exhibited by wild-type BPTI [2].
• In addition, we describe the results of calculations of C(alpha), C(beta), C(gamma)1, C(gamma)2, and C(delta) shifts in the two isoleucine residues in bovine pancreatic trypsin inhibitor and the four isoleucines in a cytochrome c and demonstrate that the side chain chemical shifts are strongly influenced by chi(2) torsion angle effects [3].
• The potential of BPIP for the treatment of pestivirus and hepacivirus infections is discussed [4].
• BPIP was inactive against the hepatitis C virus subgenomic replicon and yellow fever virus but demonstrated weak activity against GB virus [4].

Psychiatry related information on PTI

• Trypstatin has a high degree of sequence homology with human and bovine inter-alpha-trypsin inhibitors, A4(751) Alzheimer's disease amyloid protein precursor, and basic pancreatic trypsin inhibitor [5].
• The influence of reactant concentrations, temperature, reaction time and sodium borohydride on the carbohydrate residue content and the inhibiting activity of glycated aprotinin were studied [6].

High impact information on PTI

• Moreover, a single cysteine residue, tethered to the carboxy-terminal end of BPTI with a flexible linker of repeating Ser-Gly-Gly residues, is sufficient to assist in disulfide formation [7].
• Studies have been initiated to examine the "genetics" of protein folding, with mutants of bovine pancreatic trypsin inhibitor (BPTI) being used to explore the nature of the specific intramolecular interactions that direct this process [2].
• Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment [8].
• The mast cell enzyme, like a human skin chymotrypsin-like proteinase, can be distinguished from leukocyte cathepsin G by lack of susceptibility to inhibition by bovine pancreatic trypsin inhibitor [9].
• The amino-terminal sequence of the APC-binding protein exhibited considerable homology with bovine colostrum inhibitor and pancreatic trypsin inhibitor, but no apparent sequence homology with the plasma serine protease inhibitors [10].

Chemical compound and disease context of PTI

• In particular, the BPTI produced by E. coli had three disulfide bonds that appeared to be identical to those found in native BPTI, as assayed by sensitivity to iodoacetate, dithiothreitol, and urea [11].
• A mutant of bovine pancreatic trypsin inhibitor (BPTI) has been constructed and expressed in Escherichia coli in order to probe the kinetic and structural consequences of truncating the binding loop residues to alanine [12].
• A recombinant model of the reduced state of BPTI, called [R]Ala, in which all six Cys residues are replaced with Ala, has been expressed in Escherichia coli [13].
• From the linear correlation between these two parameters it was found that 5 out of the 6 tested aprotinin analogues, rTAP and r-hirudin completely inhibited thrombus formation at a therapeutical (2- to 3-fold) aPTT prolongation while 4C2, heparin and enoxaparin only inhibited thrombus formation for 40 to 50 percent at a 2-fold aPTT prolongation [14].
• A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used [15].

Biological context of PTI

• Unique-sequence synthetic DNA probes, based on the known amino acid sequence of bovine pancreatic trypsin inhibitor, were constructed from oligodeoxynucleotides [16].
• DNA sequence analysis of this clone indicated that the BPTI coding region was neither preceded by a start codon nor immediately followed by a termination codon [16].
• A synthetic probe also was used to isolate a cloned BPTI gene from a bovine genomic library [16].
• The largest changes as a result of pressure are in the loop 10-16, which contains the active site of BPTI, and residues 38-42, which are adjacent to buried water molecules [17].
• A synthetic gene encoding the protein sequence of mature bovine pancreatic trypsin inhibitor (BPTI) has been cloned into a novel E. coli expression vector [18].

Anatomical context of PTI

• Presence of pancreatic trypsin inhibitor in adrenal medullary chromaffin cells [19].
• A bovine pancreatic trypsin inhibitor was isolated from bovine adrenal medullary chromaffin granules [19].
• Partial amino acid sequencing of the purified B-43 showed that this protein was homologous to glia-derived nexin/protease nexin-1 (GDN/PN-1), plasminogen activator inhibitor 2, leukocyte elastase inhibitor (LEI) and placental thrombin inhibitor (PTI) among the serpins [20].
• In general, with the exception of aprotinin, protease inhibitors were more potent in preventing the initiation of movement than in blocking motility of demembranated spermatozoa [21].
• Isolation of pancreatic trypsin inhibitor from bovine pituitary glands [22].

Associations of PTI with chemical compounds

• Its N-terminal sequence is: arg-pro-asp-phe-cys-leu-glu-pro-pro-tyr-thr-gly-pro-cys-lys-ala-arg-ile- arg-tyr- phe-tyr-asn-ala-lys-ala-gly-leu-cys-gln-thr-phe-val-tyr-gly-gly-cys-arg- ala-lys-arg-asn-asn-phe-lys- which corresponds precisely with the N-terminus of Bovine Pancreatic Trypsin inhibitor [19].
• The specificity of BPTI for trypsin is abolished by a single amino acid exchange from lysine to isoleucine at position 15 [18].
• Some inhibitors, including aprotinin, boc-gln-leu-lys-H, and D-phe-pro-arg-H, could inhibit motility as well as prevent initiation of motility [21].
• In a previous study, a genetic screening procedure was used to identify variants of bovine pancreatic trypsin inhibitor that can fold to an active conformation but that are inactivated much more rapidly than the wild-type protein in the presence of dithiothreitol (DTT) [23].
• This occurred only in the presence of estradiol and was hampered by aprotinin and diisopropyl fluorophosphate [24].

Physical interactions of PTI

• Aprotinin did not inhibit [3H]5'-guanylylimidodiphosphate binding to FSH receptor-enriched membranes, suggesting that its effects on the affinity of the receptor for FSH and on AC activation were not mediated through an interaction with FSH receptor-associated G-protein [25].
• CONCLUSIONS: A 3-dimensional capillary network can be induced in aprotinin-stabilized FG using FGF-1 or VEGF with synergism between the 2 angiogens [26].

Enzymatic interactions of PTI

• 5. Solutions of aprotinin, modified aprotinin with the Lys15-Ala16 peptide bond cleaved and mixtures of both species were incubated with 10 mol% porcine beta-trypsin [27].

Regulatory relationships of PTI

• Bovine enterokinase was inhibited by Kunitz pancreatic trypsin inhibitor with a Kassoc of 2 X 10(8) M-1 and only weakly by other proteinase inhibitors [28].
• Sweat kallikrein had a M(r) of 40,000 and was inhibited by aprotinin but not by soybean trypsin inhibitor [29].
• Furthermore, transcytosis of S. aureus M60 across a mammary epithelial cell monolayer was significantly enhanced by the addition of bovine plasminogen and inhibited by aprotinin [30].

Other interactions of PTI

• SI was found to exist as two forms, one coinciding with authentic BPTI on western blots and the second marginally larger due to retention of the C-terminal peptide [1].
• To demonstrate the scope of the methods, MD simulations of two proteins, PTI and ubiquitin, were performed [31].
• Both aprotinin, an inhibitor of plasmin, and anti-urokinase type PA IgG blocked the generation of active TGF-beta in cultures exposed to bFGF [32].
• These include poly(L-alanine) representatives of minima corresponding to secondary and supersecondary structures, as well as poly(L-alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase [33].
• Since kallikrein is an arginine-directed serine protease, we hypothesized that an altered form of aprotinin, Arg15-aprotinin, might be a better inhibitor [34].

Analytical, diagnostic and therapeutic context of PTI

• We have investigated the binding of bovine pancreatic trypsin inhibitor (BPTI) to bovine trypsinogen by combining ultrasonic velocimetry, high precision densimetry, and fluorescence spectroscopy [35].
• The existence of such a species is supported by circular dichroism measurements on refolded BPTI [36].
• From its amino acid composition, NH2-terminal residue, mobility in paper electrophoresis, and behavior in high-performance liquid chromatography and from the tryptic pattern of the performic acid-oxidized material, it appears that the inhibitor is identical to the Kunitz and Northrop pancreatic trypsin inhibitor [22].
• Genetic dissection of pancreatic trypsin inhibitor [23].
• One of these proteases was solubilized from the plasma membranes of rat liver with 4% octyl glucoside and purified to a homogeneous state by affinity chromatography on bovine pancreatic trypsin inhibitor linked to Sepharose 4B [37].

References