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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/09/11 00:03:02」(JST)

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1. 肥満細胞由来のメディエーター mast cell derived mediators
2. アナフィラキシーの臨床診断を裏付ける臨床検査 laboratory tests to support the clinical diagnosis of anaphylaxis
3. ACE 阻害薬誘発性血管浮腫 ace inhibitor induced angioedema
4. 2型糖尿病のGlucagon-like peptide-1をベースとした治療 glucagon like peptide 1 based therapies for the treatment of type 2 diabetes mellitus
5. 高血圧のマネージメントにおけるバゾペプチターゼ阻害剤 vasopeptidase inhibition in the management of hypertension

English Journal

Crystal structures of highly specific phosphinic tripeptide enantiomers in complex with the angiotensin-I converting enzyme.

Masuyer G, Akif M, Czarny B, Beau F, Schwager SL, Sturrock ED, Isaac RE, Dive V, Acharya KR.Author information Department of Biology and Biochemistry, University of Bath, UK.AbstractHuman somatic angiotensin-I converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and a central component of the renin angiotensin aldosterone system (RAAS). Its involvement in the modulation of physiological actions of peptide hormones has positioned ACE as an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the crystal structures of the two catalytic domains of human ACE (N- and C-) in complex with FI, the S enantiomer of the phosphinic ACE/ECE-1 (endothelin converting enzyme) dual inhibitor FII, to a resolution of 1.91 and 1.85 Å, respectively. In addition, we have determined the structure of AnCE (an ACE homologue from Drosophila melanogaster) in complex with both isomers. The inhibitor FI (S configuration) can adapt to the active site of ACE catalytic domains and shows key differences in its binding mechanism mostly through the reorientation of the isoxazole phenyl side group at the P1 ' position compared with FII (R configuration). Differences in binding are also observed between FI and FII in complex with AnCE. Thus, the new structures of the ACE-inhibitor complexes presented here provide useful information for further exploration of ACE inhibitor pharmacophores involving phosphinic peptides and illustrate the role of chirality in enhancing drug specificity.
The FEBS journal.FEBS J.2013 Nov 29. doi: 10.1111/febs.12660. [Epub ahead of print]
Human somatic angiotensin-I converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and a central component of the renin angiotensin aldosterone system (RAAS). Its involvement in the modulation of physiological actions of peptide hormones has positioned ACE as an important therapeuti
PMID 24289879

A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation.

Braun JE, Truffault V, Boland A, Huntzinger E, Chang CT, Haas G, Weichenrieder O, Coles M, Izaurralde E.Author information Department of Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany.AbstractThe removal of the mRNA 5' cap structure by the decapping enzyme DCP2 leads to rapid 5'→3' mRNA degradation by XRN1, suggesting that the two processes are coordinated, but the coupling mechanism is unknown. DCP2 associates with the decapping activators EDC4 and DCP1. Here we show that XRN1 directly interacts with EDC4 and DCP1 in human and Drosophila melanogaster cells, respectively. In D. melanogaster cells, this interaction is mediated by the DCP1 EVH1 domain and a DCP1-binding motif (DBM) in the XRN1 C-terminal region. The NMR structure of the DCP1 EVH1 domain bound to the DBM reveals that the peptide docks at a conserved aromatic cleft, which is used by EVH1 domains to recognize proline-rich ligands. Our findings reveal a role for XRN1 in decapping and provide a molecular basis for the coupling of decapping to 5'→3' mRNA degradation.
Nature structural & molecular biology.Nat Struct Mol Biol.2012 Dec;19(12):1324-31. doi: 10.1038/nsmb.2413. Epub 2012 Nov 11.
The removal of the mRNA 5' cap structure by the decapping enzyme DCP2 leads to rapid 5'→3' mRNA degradation by XRN1, suggesting that the two processes are coordinated, but the coupling mechanism is unknown. DCP2 associates with the decapping activators EDC4 and DCP1. Here we show that XRN1 directl
PMID 23142987

Identification of novel inhibitors of dipeptidylcarboxypeptidase of Leishmania donovani via ligand-based virtual screening and biological evaluation.

Gangwar S, Baig MS, Shah P, Biswas S, Batra S, Siddiqi MI, Goyal N.Author information Division of Biochemistry, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Chattar Manzil Palace, PO Box 173, Lucknow 22600, India.AbstractCurrent treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations, such as high cost, toxicity, and lack of efficacy in endemic regions. Therefore, development of new, effective, and affordable anti-leishmanial drugs is a global health priority. Dipeptidylcarboxypeptidase has been characterized and established as a drug target for antileishmanial drug discovery. We virtually screened a large chemical library of 15 452 compounds against a 3D model of dipeptidylcarboxypeptidase to identify novel inhibitors. The initial virtual screening using a ligand-based pharmacophore model identified 103 compounds. Forty-six compounds were shortlisted based on the docking scores and other scoring functions. Further, these compounds were subjected to biological assay, and four of them belonging to two chemical classes were identified as the lead compounds. Identification of these novel and chemically diverse inhibitors should provide leads to be optimized into candidates to treat these protozoan infections.
Chemical biology & drug design.Chem Biol Drug Des.2012 Feb;79(2):149-56. doi: 10.1111/j.1747-0285.2011.01262.x. Epub 2011 Nov 28.
Current treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations, such as high cost, toxicity, and lack of efficacy in endemic regions. Therefore, development of new, effective, and affordable anti-leishmanial drugs is a global health priority.
PMID 22014034

Japanese Journal

亜鉛酵素の錯体化学的研究

YAKUGAKU ZASSHI 134(11), 1109-1124, 2014
NAID 130004712971

Purification and characterization of a novel prolyl endopeptidase from Aspergillus niger

Proceedings of the Japan Academy, Series B 81(10), 447-453, 2005
NAID 130000093817

Some Molecular and Inhibitory Specifications of a Dipeptidyl Carboxypeptidase from the Polychaete Neanthes virens Resembling Angiotensin I Converting Enzyme