Disease relevance of LOC396892

• Myelin basic proteins and peptides derived from them by limited cleavage with pepsin were tested for their ability to induce experimental allergic encephalomyelitis (EAE) in Lewis rats [1].
• The raised concentrations of pepsin 1 in the juice of peptic ulcer patients may thus promote the ulcerative process by increased erosion of the mucus barrier under conditions likely to pertain in the duodenal bulb as well as the stomach [2].
• Gastric juices from patients with duodenal ulcer each exhibited substantial mucolytic activity between pH 2 to 5, similar to that of pepsin 1 [2].
• 2. Amino-acid-sequence analysis was carried out by digestion of the protein with trypsin and with CNBr; some of the peptides produced were further subdigested with Staphylococcus aureus V8 proteinase or with pepsin [3].
• For example, pepsin activity of canine gastric juice is decreased by 80% after in vivo administration of 0.5 mg of the synthetic trimethyl prostanoid Ro 22-6923 per kilogram of body weight [4].

Psychiatry related information on LOC396892

• Feeding behaviors and behaviors were correlated positively to pancreas total and specific enzyme contents as well as to stomach and duodenum weights, RNA/DNA ratios of the pancreas and the stomach and protein/DNA of the pancreas but were correlated negatively with specific and total pepsin and maltase activities [5].

High impact information on LOC396892

• Salt bridges that stabilize the positioning of the N-terminal proenzyme segment across the active site of pepsin are disrupted at low pH, releasing the amino-terminal segment and thereby exposing the catalytic apparatus and the substrate-binding sites [6].
• Alignment of the amino acid sequence with that of pepsin shows regions of high homology [7].
• Penicillopepsin from Penicillium janthinellum crystal structure at 2.8 A and sequence homology with porcine pepsin [7].
• The addition of glutathione- or protein-containing sulfhydryl groups such as pepsin to the medium decreased the fluorescence [8].
• It is proposed in vivo that although adherent gastroduodenal mucus allows penetration of these agents to the underlying mucosa, it can remain in situ and continue to protect against acid (with HCO3-) and pepsin, thus minimizing mucosal damage and maximizing repair [9].

Chemical compound and disease context of LOC396892

• Pure human pepsin 1, the peptic ulcer associated pepsin, digested gastric mucus glycoprotein at a faster rate than did pure human pepsin 3 (the principal human pepsin), or the equivalent pig pepsin (pepsin A) [2].
• Systemic and mucosal immune responses of pigs to parenteral immunization with a pepsin-digested Serpulina hyodysenteriae bacterin [10].
• Mepirizole at 200 mg/kg given intraduodenally significantly reduced the volume of gastric juice but increased the acidity and pepsin activity in both pylorus-ligated and acute fistula rats [11].
• Studies are reported on the denaturation of freshly prepared, intact swine pepsin, which was inactivated by reaction with diazoacetylglycine ethyl ester, to prevent autolysis [12].

Biological context of LOC396892

• These results indicate that (i) intramolecular pepsinogen activation is accomplished by the pepsin active site, and (ii) unlike subtilisin (Carter, P., and Wells, J. A. (1988) Nature 332, 564-568), the active site mutant of pepsin is not enzymically active [13].
• Acetyl-pepsin is less effective than untreated pepsin in catalyzing transpeptidation reactions in which acetyl-L-phenylalanyl-L-tyrosine and benzyloxycarbonyl-(glycyl)n-p-nitro-L-phenylalanine are the reactants; this finding is consistent with the more rapid hydrolysis of the product of transpeptidation [14].
• Kinetics of action of pepsin on fluorescent peptide substrates [15].
• This supports the view that, in the cleavage of oligopeptide substrates by pepsin, secondary enzyme--substrate interactions may cause conformational changes at the catalytic site, and that a portion of the total binding energy may be used for the attainment of the transition state in the bond-breaking step [15].
• This effect is more marked with acetyl-pepsin than with untreated pepsin, and suggests that the conformational mobility of the active site is increased by partial acetylation [14].

Anatomical context of LOC396892

• It shows a 59% identity with the sequence of mouse submaxillary gland renin and a 49% identity with that of porcine pepsin [16].
• Biologically active preparations of 125I-thyrotropin, [3H]thyrotropin, and the [3H]exophthalmogenic factor derived from thyrotropin by partial pepsin digestion have been used to study the binding properties of the thyrotropin receptor on guinea pig retro-orbital tissue plasma membranes [17].
• This paper presents evidence for the existence in extracts from porcine non-antral gastric tissue of a peptide capable of causing substantial rises of plasma immunoreactive gastrin levels in a dose dependent manner and of stimulation of gastric acid and pepsin secretion [18].
• Pepsin digested anti-insulin serum had only an inhibitory effect on 125I-insulin binding to liver membranes [19].
• Collagen types I, II, and XI were less readily extracted from growth plate than from articular cartilage following pepsin treatment, although growth plate cartilage contains less of the mature collagen cross-links, hydroxylysyl-pyridinoline and lysyl-pyridinoline [20].

Associations of LOC396892 with chemical compounds

• D32A-pepsinogen did not convert to pepsin in acid solution but it bound to pepstatin with an apparent KD of about 5 x 10(-10) M [13].
• Gastric mucus: isolation and polymeric structure of the undegraded glycoprotein: its breakdown by pepsin [21].
• Oligopeptide substrates of porcine pepsin (E) of the type A-Phe-Phe-B (S) that are cleaved solely at the Phe-Phe bond under the conditions of these studies, and bearing an amino-terminal fluorescent probe group (mansyl or dansyl), have been used for stopped-flow measurements of the rate of formation of the A-Phe product [15].
• The disulfide bond arrangement in cathepsin D is probably similar to that of pepsin, because the positions of six half-cystine residues are conserved [22].
• Although no inhibitory activity toward any serine proteinase has been found, at least one of the uterine serpins, ovUS-1, can bind specifically to immobilized pepsin A and can weakly inhibit the proteolytic activities of pepsin A and C (but not cathepsins D and E) [23].

Enzymatic interactions of LOC396892

• Bovine and guinea pig myelin basic proteins were cleaved with pepsin at pH 3.0 or pH 6.0 (enzyme/substrate, 1:500, w/w), and the peptides were isolated and identified [24].

Other interactions of LOC396892

• It was concluded that of the residues that participate in the substrate binding, calf and pig chymosin differ in the following positions (pig pepsin numbering, subsites in parentheses): Ser 12 Thr (S4), Leu 30 Val (S1/S3), His 74 Gln (S'2), Val 111 Ile (S1/S3), Lys 220 Met (S4) [25].
• When the sequence of cathepsin D, renin, and pepsin are aligned, 32.7% of the residues are identical [22].
• ES-8891 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M [26].
• The structural stability of porcine haptocorrin after exposure to digestive enzymes (pepsin and pancreatin) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, column chromatography, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) [27].
• Rapid cleavage of bovine and guinea pig myelin basic proteins by pepsin at pH 6.0 is limited to the Phe-Phe bond in the middle of the molecule [28].

Analytical, diagnostic and therapeutic context of LOC396892

• Line 10 cells synthesized collagen type IV as judged by sensitivity to bacterial collagenase, by immunoprecipitation, by migration of pro alpha (IV) chains and pepsin-resistant fragments on sodium dodecyl sulfate-polyacrylamide gels, and by immunofluorescence [29].
• Analysis by gel filtration showed the undegraded glycoprotein was a polymer that was split into glycoprotein subunits, of about 5 X 10(5) mol wt, by pepsin and other proteolytic enzymes [21].
• Treatment of a stabilized gastric substrate with hog pepsin was found to mimic the reaction, producing immunoreactive xenopsin(s) which behaved similarly during high pressure liquid chromatography [30].
• Mutations of pepsin by site-directed mutagenesis of the Lys-319 residue were generated to study the structure-function relationships [31].
• As a new biochemical mechanism for peptide bond synthesis that has a potential for applications in biotechnology, it is here proposed that the energy necessary to drive peptide synthesis from free peptides comes from the sizable free energy drop associated with rehydration of the active site of pepsin in 55 M water [32].

References