China
Africa
Explore chapters and articles related to this topic
Intracellular Peptide Turnover: Properties and Physiological Significance of the Major Peptide Hydrolases of Brain Cytosol
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
One of the most interesting and unique features of the soluble metalloendopeptidase is its substrate specificity. The substrate specificity of most proteinases can be readily described e.g. prolyl oligopeptidase (cleavage at the carboxyl side of a proline residue), neprilysin (cleavage at the amino side of a hydrophobic amino acid), trypsin (cleavage at the carboxyl side of a basic amino acid), etc. Although soluble metalloendopeptidase-catalyzed cleavages commonly occur at the carboxyl side of a hydrophobic amino acid, neurotensin is degraded by cleavage between two arginyl residues, a His-Trp bond is one of the cleavage sites in LHRH and a Pro-Gin bond in substance P is hydrolyzed. When a series of synthetic substrates was studied, a preference for aromatic amino acid residues in the P1 and P2 positions was seen. In addition there was a marked beneficial effect when an aromatic amino acid was present in the P3’ position. The latter substituent decreased the Km and increased the kcat. It could account in part for the unusual specificity.
Presence of a neprilysin on Avicularia juruensis (Mygalomorphae: Theraphosidae) venom
Published in Toxin Reviews, 2022
Soraia Maria do Nascimento, Ursula Castro de Oliveira, Milton Yutaka Nishiyama-Jr, Alexandre Keiji Tashima, Pedro Ismael da Silva Junior
The neprilysins (NEPs) are metalloendopeptidase-type enzymes composed of approximately 750 amino acid residues (∼110 kDa) with an active site that has a zinc binding motif (El-Amouri et al. 2008). They have a high preference to cleave the N-terminal bond of hydrophobic amino acids and, in mammals, play a significant role in different biological processes like metabolism of bioactive peptides, modulation of blood pressure, control of neurotransmitter levels, cancer progression, and reproduction (Bland et al. 2008). Their presence has been observed in the venoms of the snakes Ophiophagus hannah, Echis pyramidum leakeyi, Naja kaouthia, and Crotalus horridus (this last annotated as Snake Venom Metalloproteinase) (Casewell et al. 2009, Rokyta et al. 2013, Rokyta et al. 2015, Tan et al. 2015, Tan et al. 2017, Kunalan et al. 2018); the scorpion Didymocentrus krausi (Rojas-Azofeifa et al. 2019); the jellyfish Cyanea capillata (Liu et al. 2015); and the hunting wasps Eumenes decoratus, Anterhynchium flavomarginatum, and Sphecidae sp. (Yoon et al. 2020). In spiders, the first identification of a NEP was made in the venom of Trittame loki (Undheim et al. 2013), and recently, it was also observed in the species Physocyclus mexicanus, being the most abundant component (Zobel-Thropp et al. 2019).
Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years
Published in Expert Opinion on Drug Discovery, 2019
Frances Rose, Stephen Bloom, Tricia Tan
The circulating half life of PYY3–36 is only 15 minutes [31], which limits pharmacological utility. Furthermore, the supraphysiological doses required for periodic administration of PYY to reduce food intake and induce weight loss are associated with unacceptable levels of nausea [32]. Metalloendopeptidases have been implicated in the degradation of PYY, with co-administration of actinoin, a metalloendopeptidase inhibitor, prolonging its anorectic effect [33]. This suggests that specific inhibitors or analogues of PYY that are resistant to cleavage may be useful as anti-obesity therapeutics. An alternative strategy is to use reversible polyethylene glycol (PEG)ylation, coupling PYY3–36 to a 40 kDa PEG group via a spontaneously cleavable linker, which is gradually hydrolyzed, slowly releasing unmodified PYY3–36 into the circulation [34]. Long-acting analogues of PYY are currently being tested in Phase I trials (e.g. Novo Nordisk NN-9747, Imperial College Y14 – Clinicaltrials.org NCT03673111), to establish their safety in human volunteers and to gather preliminary efficacy data.
Responses to iron oxide and zinc oxide nanoparticles in echinoderm embryos and microalgae: uptake, growth, morphology, and transcriptomic analysis
Published in Nanotoxicology, 2020
Anne-Marie Genevière, Evelyne Derelle, Marie-Line Escande, Nigel Grimsley, Christophe Klopp, Christine Ménager, Aude Michel, Hervé Moreau
Among the 196 DE contigs highly up-regulated (LFC > 3) after ZnO ENP exposure, 23 encoded proteins of the metallothionein (MT) family (w/o an assigned GO term), all of them being more severely induced upon ZnSO4 exposure (Figure S3). Seven were also up-regulated, though more weakly, in the presence of FeCl3 while none of them were stimulated by Fe2O3 ENPs. A notable effect was also observed for three contigs encoding metalloendopeptidases, MMP16 precursor, BP10 and a type IV collagenase, which are highly induced in response to zinc, either as ENP or ionic. Nine other Zn-dependent contigs encoding metalloendopeptidases were also induced, less severely, in response to both forms of zinc metal.