Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pz-peptidase was purified from chicken liver as a protein of Mr 80,000 and pI 5.2. The purified enzyme hydrolysed phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg, 2,4-dinitrophenyl-Pro-Leu-Gly-Pro-Trp-D-Lys. 7-methoxycoumarin-3-carboxylyl-Pro-Leu-Gly-Pro-D-(2,4-dinitropheny l)Lys, benzoyl-Gly-Ala-Ala-Phe-p-aminobenzoate, Ac-Ala4 (at the Ala-1-Ala-2 bond) and bradykinin (at the Phe-5-Ser-6 bond). No hydrolysis of proteins was detected. Loss of activity in the presence of EDTA or 1,10-phenanthroline was time-dependent. Metal ions found to restore activity after treatment with EDTA were Zn2+, Mn2+, Ca2+, Co2+ and Cd2+, in decreasing order of effectiveness. Ni2+, Fe2+ and higher concentrations of Zn2+ were inhibitory. Inhibition by N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate and related compounds showed Ki values (down to 5 nM) somewhat lower than those for the rat enzyme. Pz-peptidase was activated by low concentrations of 2-mercaptoethanol and dithiothreitol, but inhibited by higher concentrations. p-Chloromercuribenzoate and some other thiol-blocking reagents were inhibitory. Inactivation by diethyl pyrocarbonate that was reversible by hydroxylamine showed the presence of essential histidine residue(s). We conclude that chicken Pz-peptidase is a metallo-endopeptidase with thiol-dependence. Moreover, the properties of chicken Pz-peptidase agree with those described for mammalian soluble metallo-endopeptidase and endo-oligopeptidase A. consistent with the view that these three types of activity are all attributable to the single enzyme for which the name thimet peptidase has been proposed.
 ...
PMID:Chicken liver Pz-peptidase, a thiol-dependent metallo-endopeptidase. 185 43

Rat kidney neutral endopeptidase 24.11, "enkephalinase", was rapidly inactivated by diethyl pyrocarbonate under mildly acidic conditions. The pH dependence of inactivation revealed the modification of an essential residue with a pKa of 6.1. The reaction of the unprotonated group with diethyl pyrocarbonate exhibited a second-order rate constant of 11.6 M-1 s-1 and was accompanied by an increase in absorbance at 240 nm. Treatment of the inactivated enzyme with 50 mM hydroxylamine completely restored enzyme activity. These findings indicate histidine modification by diethyl pyrocarbonate. Comparison of the rate of inactivation with the increase in absorbance at 240 nm revealed a single histidine residue essential for catalysis. The presence of this histidine at the active site was indicated by (a) the protection of enzyme from inactivation provided by substrate and (b) the protection by the specific inhibitor phosphoramidon of one histidine residue from modification as determined spectrally. The dependence of the kinetic parameter Vmax/Km upon pH revealed two essential residues with pKa values of 5.9 and 7.3. It is proposed that the residue having a kinetic pKa of 5.9 is the histidine modified by diethyl pyrocarbonate and that this residue participates in general acid/base catalysis during substrate hydrolysis by neutral endopeptidase 24.11.
 ...
PMID:Evidence for an essential histidine in neutral endopeptidase 24.11. 347 91

Diethylpyrocarbonate treatment of the neutral endopeptidase (EC 3.4.24.11) inhibits both catalytic activity and binding of the inhibitor [3H]-N(R,S)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-glycine. The loss of activity can be reversed by hydroxylamine and almost completely prevented by the competitive inhibitor phenylalanyl-leucine suggesting the presence, as in thermolysin, of a histidine residue at the active site. Butanedione treatment also reduces both catalytic activity and [3H] inhibitor binding. Phenylalanyl-leucine completely protects from the butanedione induced loss of activity, providing further evidence for an essential arginine at the active site. In contrast, the tyrosine modifying agent N-acetylimidazole has no apparent effect on enzyme activity.
 ...
PMID:Presence of a histidine at the active site of the neutral endopeptidase-24.11. 353 67

Four primary zinc-binding pharmacophores (thiols, carboxylates, phosphorus acids, and hydroxamates) have been utilized in generating inhibitors of zinc metalloproteases such as ACE, NEP, the MMPs, and ECE. Although compounds which inhibit the activity of both ACE and NEP (vasopeptidase inhibitors, VPIs) have been reported which incorporate a thiol, carboxylate, or phosphorus acid pharmacophore, the generation of hydroxamate based vasopeptidase inhibitors has remained elusive. Herein we report the first potent vasopeptidase inhibitors which were generated from the incorporation of conformationally restricted dipeptide mimetics to an N-formyl hydroxylamine zinc-binding group. Compounds such as 13c and 13d are among the most potent in this series, exhibiting in vitro activity comparable to other classes of inhibitors.
 ...
PMID:N-formyl hydroxylamine containing dipeptides: generation of a new class of vasopeptidase inhibitors. 1069 48

The amino acid sequence of a bradykinin-releasing enzyme, named KR-E-1, isolated from the venom of Agkistrodon caliginosus (Kankoku-mamushi) was determined by Edman sequencing of the peptides which was derived from digests with cyanogen bromide, hydroxylamine, achromobacter protease I, trypsin, V8 protease, arginine endopeptidase, and endoproteinase Asp-N. KR-E-1 consisted of 235 amino acids and showed conservation of the catalytic amino acid residues (His(57), Asp(102), and Ser(195)) of the chymotrypsin family of serine protease in its amino acid sequence. The carboxy-terminal amino acid, Phe, was determined using carboxypeptidase Y. This enzyme contains glucosamine and an N-linked glycosylation site. KR-E-1 showed 32, 31, 65, 65, and 67% sequence homology to human kallikrein, bovine thrombin, KN-BJ 2, elegaxobin, and elegaxobin II, respectively. The characteristic of structure of KR-E-1 was found to involve hydrophobic amino acid residues abundantly localizing in positions 1-50, with lysine residues abundantly localizing in positions 73-101.
 ...
PMID:Amino acid sequence of a kinin-releasing enzyme, KR-E-1, from the venom of Agkistrodon caliginosus (Kankoku-mamushi). 1872 43