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)

Neuropeptides containing the carboxylterminal sequence Arg-Phe-NH2 are found throughout the animal kingdom and are important substances mediating neuronal communication. Here, we have cloned the cDNA coding for the precursor protein of the sea anemone neuropeptide (Antho-RFamide) less than Glu-Gly-Arg-Phe-NH2. This precursor is 334 amino acids in length and contains 19 copies of unprocessed Antho-RFamide (Gln-Gly-Arg-Phe-Gly), which are tandemly arranged in the C-terminal part of the protein. Paired basic residues (Lys-Arg) or single basic residues (Arg) occur at the C-terminal side of each Antho-RFamide sequence. These are likely signals for posttranslational cleavage. The processing signals at the N-terminal side of each Antho-RFamide sequence, however, include acidic residues. Processing at these amino acids must involve either an amino- or an endopeptidase that cleaves C-terminally of aspartic acid or glutamic acid residues. Such processing is, to our knowledge, hitherto unknown for peptidergic neurons. The Antho-RFamide precursor also contains two copies of the putative Antho-RFamide-related peptide Phe-Gln-Gly-Arg-Phe-NH2 and one copy of Tyr-Val-Pro-Gly-Arg-Tyr-NH2. In addition, the precursor protein harbors four other putative neuropeptides that are much less related to Antho-RFamide. This report shows that the biosynthetic machinery for neuropeptides in coelenterates, the lowest animal group having a nervous system, is already very efficient and similar to that of higher invertebrates, such as mollusks and insects, and vertebrates.
 ...
PMID:Primary structure of the precursor for the sea anemone neuropeptide Antho-RFamide (less than Glu-Gly-Arg-Phe-NH2). 170 27

The production of enkephalin (EK) in the rat dental pulp was studied in pharmacological and biochemical aspects of EK-producing enzyme, EK precursor protein and the regulation of EK production. The EK precursor protein was primarily distributed in the microsomal fraction, and a common precursor protein (Mr about 58,000) was partially purified by Sephadex G-100 chromatography. Since the EK-producing enzyme, however, was mainly localized in the lysosomal fraction, and was found to be a cysteine proteinase, the lysosomal cysteine proteinases, cathepsins H, B and L, were separated by CM Sephadex C-50 ion exchange chromatography, and identified in respects to substrate specificity, pH optimum and inhibitor sensitivity. The EK-producing activity of the cathepsin B was demonstrated using the partially purified EK precursor protein from the pulp tissue as a substrate. The cathepsin B was further purified by Sephadex G-75 gel filtration to a 400-fold purity, and SDS polyacrylamide gel electrophoresis of the enzyme showed a distinct homogeneity (Mr about 23,600). The purified enzyme cleaved BAM-12P, a met-EK-containing peptide from bovine adrenal medulla, to met-EK-Arg6, but did not convert met-EK-Arg6 to met-EK, suggesting an endopeptidase activity of the enzyme. On the other hand, a concentration-dependent activation of the enzyme by bradykinin (BK) and des-Arg9-BK was found to be mediated through B1 receptor in intact pulp tissue. It was also demonstrated that intact structure of lysosomes and Ca++ were necessary for the activation of the enzyme by BK.
 ...
PMID:Pharmacological and biochemical study on the mechanism of enkephalin production in rat dental pulp. 213 Jan 76

Achromobacter protease I (API) is a lysine-specific serine protease which hydrolyzes specifically the lysyl peptide bond. A gene coding for API was cloned from Achromobacter lyticus M497-1. Nucleotide sequence of the cloned DNA fragment revealed that the gene coded for a single polypeptide chain of 653 amino acids. The N-terminal 205 amino acids, including signal peptide and the threonine/serine-rich C-terminal 180 amino acids are flanking the 268 amino acid-mature protein which was identified by protein sequencing. Escherichia coli carrying a plasmid containing the cloned API gene overproduced and secreted a protein of Mr 50,000 (API') into the periplasm. This protein exhibited a distinct endopeptidase activity specific for lysyl bonds as well. The N-terminal amino acid sequence of API' was the same as mature API, suggesting that the enzyme retained the C-terminal extended peptide chain. The present experiments indicate that API, an extracellular protease produced by gram-negative bacteria, is synthesized in vivo as a precursor protein bearing long extended peptide chains at both N and C termini.
 ...
PMID:Cloning, nucleotide sequence, and expression of Achromobacter protease I gene. 268 82

Fluorogenic peptide substrates designed to encompass the reported alpha-secretory and amyloidogenic cleavage sites of the amyloid-beta precursor protein (beta PP) were used to analyze proteinase activities in brain extracts from control patients and those with Alzheimer's disease (AD). Activity against the secretory substrate at pH 7.5 in control and AD brains produced a major endopeptidase cleavage at the Lys687-Leu688 bond (beta PP770 numbering), consistent with the beta PP secretase cleavage. Activity in control brains against the amyloidogenic substrate at pH 7.5 produced one cleavage at the Ala673-Glu674 bond, two residues C-terminal to the amyloidogenic Met-Asp site. However, in three of four AD brains, the major cleavage was at the Asp-Ala bond, one residue from the amyloidogenic site. Both endopeptidase and carboxypeptidase activities in AD brains were lower than in control brains. Proteinase activities against the secretory substrate had a major optimum at pH 3.0-4.0 and another at pH 6.0-7.5. Proteinase activities against the amyloidogenic substrate had a major optimum at or below pH 3.0 and another at pH 6.0. Using both substrates, activities at low pH were higher in AD-brains than in controls, while at pH above 6.5, activities in control brains were higher than in AD. These results indicate that the levels of proteolytic enzymes in AD brains are altered relative to controls.
 ...
PMID:Potential beta PP-processing proteinase activities from Alzheimer's and control brain tissues. 798 41

Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory agent produced primarily by activated monocytes and macrophages. TNF-alpha is synthesized as a precursor protein of M(r) 26,000 (26K) which is processed to a secreted 17K mature form by cleavage of an Ala-Val bond between residues 76-77. The enzyme(s) responsible for processing pro-TNF-alpha has yet to be identified. Here, we describe the capacity of a metalloproteinase inhibitor, GI 129471, to block TNF-alpha secretion both in vitro and in vivo. The inhibition is specific to TNF-alpha; the production of other secreted cytokines, such as the interleukins IL-1 beta, IL-2, or IL-6, is not inhibited. The mechanism of inhibition occurs at a post-translational step in TNF-alpha production. Our data suggest that TNF-alpha processing is mediated by a unique Zn2+ endopeptidase which is inhibited by GI 129471 and would represent a novel target for therapeutic intervention in TNF-alpha associated pathologies.
 ...
PMID:Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. 805 11

A processing protease for the human immunodeficiency virus type I (HIV-I) envelope glycoprotein gp160 precursor has been purified to homogeneity from the post-nuclear membrane fraction of a human T4+ lymphocyte clone. Most of the processing activity was found to be present in the fractions of endoplasmic reticulum and Golgi apparatus of the cells. The purified enzyme has a monomeric structure with a molecular mass of 26 +/- 3 kDa, as judged by gel-permeation liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions. The purified enzyme converted gp160 to gp120 and gp41, showing a pH optimum of 6.5-7.0. Direct amino acid sequencing of the amino terminus of the product gp41 revealed that the cleavage site of gp160 was between Arg511 and Ala512. The enzyme activity was inhibited by trypsin-type protease inhibitors, but was not affected by CaCl2, MgCl2 or chelating agents. The properties of the purified enzyme are clearly distinct from those of processing proteases reported previously. Although the significance of the enzyme in vivo is not currently certain, judging from its cleavage specificity and subcellular localization, this endopeptidase appears to be a processing enzyme for the human immunodeficiency virus type I gp160 precursor protein in human T cells.
 ...
PMID:Processing protease for gp160 human immunodeficiency virus type I envelope glycoprotein precursor in human T4+ lymphocytes. Purification and characterization. 809 9

We describe a new member of the receptor protein tyrosine phosphatase family, R-PTP-kappa, cDNA cloning predicts that R-PTP-kappa is synthesized from a precursor protein of 1,457 amino acids. Its intracellular domain displays the classical tandemly repeated protein tyrosine phosphatase homology, separated from the transmembrane segment by an uncharacteristically large juxta-membrane region. The extracellular domain of the R-PTP-kappa precursor protein contains an immunoglobulin-like domain and four fibronectin type III-like repeats, preceded by a signal peptide and a region of about 150 amino acids with similarity to the Xenopus A5 antigen, a putative neuronal recognition molecule (S. Takagi, T. Hsrata, K. Agata, M. Mochii, G. Eguchi, and H. Fujisawa, Neuron 7:295-307, 1991). Antibodies directed against the intra- and extracellular domains reveal that the R-PTP-kappa precursor protein undergoes proteolytic processing, following which both cleavage products remain associated. By site-directed mutagenesis, the likely cleavage site was shown to be a consensus sequence for cleavage by the processing endopeptidase furin, located in the fourth fibronectin type III-like repeat. In situ hybridization analysis indicates that expression of R-PTP-kappa in the central nervous system is developmentally regulated, with highest expression seen in actively developing areas and, in the adult, in areas capable of developmental plasticity such as the hippocampal formation and cerebral cortex. The mouse R-PTP-kappa gene maps to chromosome 10, at approximately 21 centimorgans from the centromere.
 ...
PMID:Cloning and characterization of R-PTP-kappa, a new member of the receptor protein tyrosine phosphatase family with a proteolytically cleaved cellular adhesion molecule-like extracellular region. 847 52

The isolation and sequence determination of a new 2S albumin storage protein from Ricinus communis seeds denoted 2S ASP-Ib are described. The fragment approach using selective enzymatic cleavage, Edman degradation, and mass spectrometry was used to demonstrate that the 11-kDa heterodimer protein linked by disulfide bridges has the following structure: short chain, GEREGSSSQQCRQEVQRKDLSSCERYLRQSSS; long chain, <QQQESQQLQQCCNQVKQVRDECQCEAIKYIAEDQIQQGQLHGEESERVAQRAGEIVSSCGVRCMR . The molecular weight of the intact protein, 11,140 +/- 2, determined by matrix-assisted laser desorption mass spectrometry was consistent with the assigned structure. The S- and L-chains are identical to residues 18-49 and 66-130 of the precursor protein predicted by S. D. Irwin, J. N. Keen, J. B. C. Findlay, and J. M. Lord [(1990) Mol. Gen. Genet. 222, 400-408], on the basis of the structure of a cDNA isolated using probes based on the sequence of another 2S albumin, described by F. S. Sharief and S. S. L. Li [(1982) J. Biol. Chem. 257, 14753-14759], which we denote 2S ASP-Ia. Three of the four termini could have been produced by posttranslational processing by endopeptidase(s) and carboxypeptidase(s) which utilized basic residues as the cleavage sites. Mass spectrometric evidence suggested that the protein presented microheterogeneity at its termini, i.e., truncated forms presumably due to processing heterogeneity. The present characterization of the 2S ASP-Ib protein, the second 2S albumin from Ricinus communis seeds, demonstrates that the 237-residue precursor protein codes for two different heterodimer proteins containing 97 and 99 residues each. This system should be useful for studying the posttranslational processing of plant storage proteins.
 ...
PMID:Amino acid sequence of a new 2S albumin from Ricinus communis which is part of a 29-kDa precursor protein. 895 Oct 29

A novel staphylolytic enzyme, ALE-1, acting on Staphylococcus aureus, was purified from a Staphylococcus capitis EPK1 culture supernatant. The optimal pH range for staphylolytic activity was 7 to 9. ALE-1 contains one Zn2+ atom per molecule. Analysis of peptidoglycan fragments released by ALE-1 indicated that the enzyme is a glycylglycine endopeptidase. The effects of various modulators were determined, and we found that o-phenanthroline, iodoacetic acid, diethylpyrocarbonate, and Cu2+ reduced the staphylolytic activity of ALE-1. beta-Casein, elastin, and pentaglycine were poor substrates for ALE-1. Molecular cloning data revealed that ALE-1 is composed of 362 amino acid residues and is synthesized as a precursor protein which is cleaved after Ala at position 35, thus producing a mature ALE-1 of 35.6 kDa. The primary structure of mature ALE-1 is very similar to the proenzyme form of lysostaphin. It has the modular design of an N-terminal domain of tandem repeats of a 13-amino-acid sequence fused to the active site containing C-terminal domain. Unlike lysostaphin, ALE-1 does not undergo processing of the N-terminal repeat domain in broth culture. ale-1 is encoded on the plasmid. Protein homology search suggested that ALE-1 and lysostaphin are members of the novel Zn2+ protease family with a homologous 38-amino-acid-long motif, Tyr-X-His-X(11)-Val-X(12/20)-Gly-X(5-6)-His.
 ...
PMID:Purification and molecular characterization of glycylglycine endopeptidase produced by Staphylococcus capitis EPK1. 902 2

A new lysyl endopeptidase producing strain, Lysobacter sp. IB-9374, was isolated from soil. This strain secreted the endopeptidase to culture medium at 6-12-fold higher levels relative to Achromobacter lyticus and Lysobacter enzymogenes. The mature Lysobacter sp. enzyme was enzymatically identical to Achromobacter lysyl endopeptidase bearing lysyl bond specificity, a high peptidase activity, a wide pH optimum, and stability against denaturants. Nucleotide sequence analysis of the Lysobacter sp. lysyl endopeptidase gene revealed that the enzyme is synthesized as a precursor protein consisting of signal peptide (20 amino acids (aa)), pro-peptide (185 aa), mature enzyme (268 aa), and C-terminal extension peptide (198 aa). The deduced amino acid sequence of the mature enzyme was totally identical to that of the Achromobacter enzyme. The Lysobacter sp. precursor protein has an 18-aa longer peptide chain following nine consecutive amino acid residues distinct from the Achromobacter counterpart at the C-terminus. Total precursor protein is 671 aa of which only 268 aa are in the finally processed exoenzyme.
 ...
PMID:Lysobacter strain with high lysyl endopeptidase production. 1212 82


1 2 3 Next >>