Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extended substrate binding sites of several chymotrypsin-like serine proteases, including rat mast cell proteases I and II (RMCP I and II, respectively) and human and dog skin chymases, have been investigated by using peptide 4-nitroanilide substrates. In general, these enzymes preferred a P1 Phe residue and hydrophobic amino acid residues in P2 and P3. A P2 Pro residue was also found to be quite acceptable. The S4 subsites of these enzymes are less restrictive than the other subsites investigated. The substrate specificity of these enzymes was also investigated by using substrates which contain model desmosine residues and peptides with amino acid sequences of the physiologically important substrates angiotensin I and angiotensinogen and alpha 1-antichymotrypsin, the major plasma inhibitor for chymotrypsin-like enzymes. These substrates were less reactive than the most reactive tripeptide reported here, Suc-Val-Pro-Phe-NA. The thiobenzyl ester Suc-Val-Pro-Phe-SBzl was found to be an extremely reactive substrate for the enzymes tested and was 6-171-fold more reactive than the 4-nitroanilide substrate. The four chymotrypsin-like enzymes were inhibited by chymostatin and N-substituted saccharin derivatives which had KI values in the micromolar range. In addition, several potent peptide chloromethyl ketone and substituted benzenesulfonyl fluoride irreversible inhibitors for these enzymes were discovered. The most potent sulfonyl fluoride inhibitor for RMCP I, RMCP II, and human skin chymase, 2-(Z-NHCH2CONH)C6H4SO2F, had kobsd/[I] values of 2500, 270, and 1800 M-1 s-1, respectively. The substrates and inhibitors reported here should be extremely useful in elucidating the physiological roles of these proteases.
 ...
PMID:Mammalian chymotrypsin-like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4-nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors. 389 42

Digestive gland protease pH optima and specific activities determined in Penaeus indicus with casein, azocasein, Azocoll, and Congo red fibrin as substrates were pH 7.7-9.2, 210-371 micromol of tyrosine/mg of homogenate protein/min; pH 7.8, 36; pH 6.0-7.0, 7; and pH 8.9-9.2, 7A delta0.001 U/mg of homogenate protein/min, respectively. Activity in the shrimp was stable during frozen storage but relatively labile and very low (1.043 azocasein units) in the Norwegian lobster, Nephrops norvegicus. The high activity in shrimp is significant in aquaculture and may be a source of proteolytic enzymes for industrial use. The rapid deterioration after landing may be a consequence of the high and stable activity. The low activity in the lobster may present a problem in culture and requires a more critical choice of feed as well as further investigation. 4-(2-Aminoethyl)-benzenesulfonyl fluoride hydrochloride was a very convenient, fast-acting, and effective inhibitor of shrimp trypsin and chymotrypsin but did not completely inhibit general protease activity in shrimp and had a negligible effect on the lobster. A significant component of that activity may be from nonserine proteases (such as the exoproteases carboxypeptidase A and B and the leucine aminopeptidases), whose proportion relative to the serine proteases may be greater in the lobster.
 ...
PMID:Studies on digestive proteases from midgut glands of a shrimp, Penaeus indicus, and a lobster, Nephrops norvegicus: Part 1. Proteolytic activity. 1129 89