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

[1-Sarcosine,4-beta-homotyrosine]-(I), [5-beta-homoisoleucine]-(II), and [1-sarcosine,5-beta-homoisoleucine]angiotensin II (III) were synthesized by Merrifield's solid-phase procedure to study the effect of pressor activity and duration of action. The analogues I--III possessed, respectively, 1.98, 2.82, and 29.2% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats by single-injection procedure) and duration of action of 5.5, 6.7, and 4.7 min; the comparative duration of action of an equipressor dose of angiotensin II was 5.2, 6.3, and 5.3 min, respectively. When incubated with leucine aminopeptidase, degradation of II was as fast as that of angiotensin II; this degradation became considerably slower when position 1 was replaced with sarcosine. Incubation of all these analogues with chymotrypsin showed very little or no degradation up to 3 h. The results indicate that an increase in the chain length by one carbon atom in position 4 or 5 of angiotensin II increased resistance to degradation by chymotrypsin without any increase in in vivo duration of action. Further, all analogues showed low pressor activity.
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PMID:Synthesis of angiotensin II analogues by incorporating beta-homotyrosine or beta-homoisoleucine residues. 49 May 61

Sarcosine oxidase from Corynebacterium sp. U-96 is inhibited by iodoacetamide (IAM) and the inhibition is prevented by the substrate analog, sodium acetate. To elucidate the mechanism of inhibition of the enzyme by IAM, we determined the amino acid sequences around the IAM-reactive cysteine residues, and the effects of the modification on the enzyme activity and the oxidation-reduction of the FAD moieties of the enzyme. The enzyme was specifically labeled with [14C]IAM, and the labeled subunit B was digested with trypsin and chymotrypsin. The HPLC profiles of the proteolytic digests showed mainly two radioactive peaks. The 14C-labeled peptides were purified, and their N-terminal sequences were determined to be Cys-Gly-Thr-Pro-Gly-Ala-Gly-Tyr (TC-1) and Ala-Gly-Ile-Ala-Cys-Xaa-Asp-Xaa-Val-Ala(-)- (TC-2). Peptide TC-2 contains a covalent FAD-binding sequence [Asx-His-Val-Ala; Shiga et al. (1983) Biochem. Int., 6, 737]. [14C]IAM-incorporation into the TC-1 sequence was strongly inhibited by sodium acetate. The N-terminal amino acid sequence of the CNBr fragment containing the TC-1 sequence (65 residues) was determined. According to the secondary structure predictions, Gly-Thr-Pro-Gly-Ala-Gly of the TC-1 sequence is located between the beta sheet and alpha helix of the sequence, indicating the presence of an AMP-binding site in the TC-1 region. The activity of the enzyme treated with IAM in the presence and absence of sodium acetate was not inhibited by sodium sulfite, which is known to react specifically with covalent FAD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cysteine residues in the active site of Corynebacterium sarcosine oxidase. 193 12