Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of alpha-chymotrypsin and alpha-lytic protease with chloro(2,2':6',2''-terpyridine)platinum(II), [Pt(trpy)Cl]+, results in attachment of Pt(trpy)2+ tags at both His 57 and His 40 in the former and His 57 in the latter. The [Pt(trpy)His]2+ chromophores are readily detected and quantitated owing to their characteristic, strong UV absorption. Although the tagging of His 57 modifies the catalytic triad (Ser 195, His 57, and Asp 102) and disrupts the charge relay, the platinated enzymes retain significant esterase and amidase activity for both specific and nonspecific substrates. Unlike suicide inhibitors, which inactivate the enzymes by filling the active site and imitating the tetrahedral intermediate, [Pt(trpy)Cl]+ reacts with a particular amino acid and permits binding of substrates. The kinetic constants for the following are reported: two esters and two amides with alpha-chymotrypsin and an amide with alpha-lytic protease. The kcat values are between 1 and 25% of, and the Km values are a little higher than, the corresponding values for the native enzymes. The catalytic activity is not due to the native enzymes, trypsin, or some zinc-containing protease. Activities of the native and of the platinated alpha-chymotrypsin depend similarly on pH although the pKa of His 57 is raised to 9.7 upon platination. The platinated enzymes undergo autodigestion slower than do the native enzymes. Because the Pt(trpy)2+ tags are noninvasive, stable, and yet easily removable by thiourea, [Pt(trpy)Cl]+ may be used to retard autodigestion of stored proteolytic enzymes.
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PMID:Catalytic activity of the serine proteases alpha-chymotrypsin and alpha-lytic protease tagged at the active site with a (terpyridine)platinum(II) chromophore. 222 78

After partial reduction of disulfide bonds in the thaumatins, the sweet-tasting proteins from the fruits of Thaumatococcus danielii Benth, a rapid autodigestion was demonstrated. In the presence of suitable substrates, the reduced thaumatins showed protease, amidase and esterase activity. Thiol-blocking reagents like mercury(II) chloride inhibited the enzymatic activity. Of the thaumatins b, c, I, II and III (with increasing isoelectric points), thaumatin I showed the lowest enzymatic activity. In this series, the enzymatic activity increased from thaumatin I to thaumatin III as well as from thaumatin I to thaumatin b. Acetylation of the epsilon-amino group of lysine residues in the thaumatins by acetic anhydride, causing a decrease in basicity, led to an increase in enzymatic activity, which is correlated with the number of acetyl groups introduced. Comparison of the amino acid sequence of thaumatin I with that of cysteine proteases of plant origin showed no similarities. Moreover, the thaumatins lack histidine, one of the amino acids in the active site of the cysteine proteases. Monellin, the sweet-tasting protein from the fruits of Dioscoreophyllum cumminsii Diels, is not enzymatically active. However, when monellin with acetylated epsilon-amino groups of lysine residues was brought into a reducing environment it appeared to be enzymatically active. The similarities in properties of the thaumatins and monellin suggest a structural relationship between these proteins.
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PMID:Enzymatic properties of the sweet-tasting proteins thaumatin and monellin after partial reduction. 698 15

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.
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PMID:Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. 884 Nov 72

Protease IV is a lysine-specific endoprotease produced by Pseudomonas aeruginosa whose activity has been correlated with corneal virulence. Comparison of the protease IV amino acid sequence to other bacterial proteases suggested that amino acids His-72, Asp-122, and Ser-198 could form a catalytic triad that is critical for protease IV activity. To test this possibility, site-directed mutations by alanine substitution were introduced into six selected residues including the predicted triad and identical residues located close to the triad. Mutations at any of the amino acids of the predicted catalytic triad or Ser-197 caused a loss of enzymatic activity and absence of the mature form of protease IV. In contrast, mutations at His-116 or Ser-200 resulted in normal processing into the enzymatically active mature form. A purified proenzyme that accumulated in the His-72 mutant was shown in vitro to be susceptible to cleavage by protease IV purified from P. aeruginosa. Furthermore, similarities of protease IV to the lysine-specific endoprotease of Achromobacter lyticus suggested three possible disulfide bonds in protease IV. These results identify the catalytic triad of protease IV, demonstrate that autodigestion is essential for the processing of protease IV into a mature protease, and predict sites essential to enzyme conformation.
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PMID:Identification of the active site residues of Pseudomonas aeruginosa protease IV. Importance of enzyme activity in autoprocessing and activation. 1241 15

An 82-year-old man presented with a two-week history of three painful, inflamed nodules on his lower extremities with symmetric arthritis of multiple joints. He was under the care of hospice for end-stage acinar cell carcinoma of the pancreas. His serum amylase and lipase levels were markedly elevated. An incisional biopsy revealed lobular inflammation of subcutaneous fat, focal fat necrosis with saponification/ghost cells and scattered foreign-body type giant cells consistent with pancreatic fat necrosis/pancreatic panniculitis. This is hypothesized to be initiated by autodigestion of subcutaneous fat secondary to systemic spillage of excess digestive pancreatic enzymes. Enzymes such as amylase, lipase and trypsin are increased in the bloodstream and can affect remote tissues, such as the subcutaneous fat and articular surfaces of joints. This report, along with the patient's clinical findings, was consistent with PPP syndrome: pancreatic disease, polyarthritis and panniculitis. Although the pancreatic disease of PPP syndrome usually includes pancreatitis, this case represents a report of polyarthritis and panniculitis occurring in the presence of pancreatic carcinoma.
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PMID:Subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome. 2086 49