Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (8 Hz, 1 msec, 12 V for 15 sec) of guinea pig trachea desensitized with capsaicin (1 microM), pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. These relaxations averaged 60 to 80% of the contractions to histamine. The relaxations were inhibited markedly by the addition of the nitric oxide (NO) synthase inhibitor L-nitro-n-arginine (L-NNA)(30 microM), suggesting that these relaxations are due to the release of NO. The inhibition produced by L-NNA was reversed by either L-arginine or L-citrulline. L-Citrulline was both more potent and efficacious than L-arginine in this regard. The ability of L-citrulline to reverse the inhibition produced by L-NNA was not altered by L-glutamine (1 mM). The addition of L-citrulline (1 mM) added before L-NNA was without effect on the relaxant responses to field stimulation but was able to prevent the inhibition produced by L-NNA. L-Citrulline also reversed the inhibition produced by another NO synthase inhibitor, L-nitro monomethyl arginine. Relaxations to field stimulation (16 Hz, 1 msec, 12 V for 15 sec) of human bronchus also were inhibited by 30 microM L-NNA and, as in the guinea pig, this inhibition by L-NNA could be reversed by L-citrulline. These results suggest that L-citrulline is able to overcome the inhibition of NO synthase by NO synthase inhibitors in the guinea pig trachea and human bronchus.
 ...
PMID:L-citrulline reverses the inhibition of nonadrenergic, noncholinergic relaxations produced by nitric oxide synthase inhibitors in guinea pig trachea and human bronchus. 751 67

The S' subsite specificity of four homologous serine proteases, rat chymotrypsin, rat trypsin, alpha-lytic protease, and cercarial protease from Schistosoma mansoni, was studied by measuring acyl-transfer reactions to 100 pentapeptide nucleophiles. Peptides of the general structures H-Xaa-Ala-Ala-Ala-Ala-NH2, H-Ala-Xaa-Ala-Ala-Ala-NH2, and H-Ala-Ala-Xaa-Ala-Ala-NH2 were synthesized, where Xaa is D-Ala, Cit, and all natural amino acids except Cys. The variable residues of these nucleophiles occupy the P'1, P'2, and P'3 positions in acyl-transfer reactions. The P'1 and P'2 residues were found to influence the efficiency of the nucleophiles by more than 2 orders of magnitude, whereas the S'3 subsite shows a lower specificity in all four enzymes. We synthesized consensus peptides of the general structure H-aa1-aa2-aa3-Ala-Ala-NH2, in which two or three positions were occupied by amino acids that showed the highest specificity in the first series of nucleophiles. Peptides with optimal amino acid residues in the P'2 and P'3 positions show a very high efficiency in chymotrypsin- and trypsin-catalyzed reactions. Otherwise, large specific side chains in the P'1 and P'3 positions of the nucleophiles show less than additive binding contributions due to steric hindrance. Comparison of chymotrypsin-catalyzed acyl-transfer reactions to nucleophiles of the structures H-Xaa-Leu-Arg-Ala-Ala-NH2 and H-Xaa-Ala-Ala-Ala-Ala-NH2 reveals a significantly different P'1 specificity for both series which confirms steric hindrance between large P'1 and P'3 residues.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of the S' subsites in serine protease catalysis. Active-site mapping of rat chymotrypsin, rat trypsin, alpha-lytic protease, and cercarial protease from Schistosoma mansoni. 815 42

Nucleophilic efficiency of the free amino acids in chymotrypsin-catalyzed acyl transfer in ice at -18 degrees C using ethyl esters of N-maleyl-L-tyrosine and L-tyrosine as the acyl group donors has been studied. Although the amino acids did not act as acyl acceptors in liquid water, the high yields of peptides were obtained in frozen solutions at pH 10.5 (before freezing). The efficiency of amino acids in the formation of the corresponding dipeptides depended on the substrate used, and decreased in the order Ser,Thr,Gln > Lys > Cit > Ala > Ala > Gly > Asn > Arg > Glu > Val > Orn > Asp with no peptide formed with His, Leu, Ile and Pro) for N-maleyl-L-tyrosine ethyl ester and Ser > Lys > Orn > Arg,Cit > Gln > Thr > Asn > Ala > Gly (with no peptide formed with Glu, Val, Asp, His, Leu, Ile and Pro) for L-tyrosine ethyl ester.
 ...
PMID:Peptide synthesis by chymotrypsin in frozen solutions. Free amino acids as nucleophiles. 835 4