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Titolo:
NMR structure of a minimized human agouti related protein prepared by total chemical synthesis
Autore:
Bolin, KA; Anderson, DJ; Trulson, JA; Thompson, DA; Wilken, J; Kent, SBH; Gantz, I; Millhauser, GL;
Indirizzi:
Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA Univ Calif Santa Cruz Santa Cruz CA USA 95064 m, Santa Cruz, CA 95064 USA Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 , Dept Surg, Ann Arbor, MI 48109 USA Gryphon Sci, S San Francisco, CA 94080 USA Gryphon Sci S San Francisco CAUSA 94080 i, S San Francisco, CA 94080 USA
Titolo Testata:
FEBS LETTERS
fascicolo: 2, volume: 451, anno: 1999,
pagine: 125 - 131
SICI:
0014-5793(19990521)451:2<125:NSOAMH>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
SECONDARY STRUCTURE; 3-DIMENSIONAL STRUCTURES; MELANOCORTIN RECEPTORS; OBESITY; GENE; MICE; SPECTROSCOPY; ANTAGONIST; EXPRESSION; RESTRAINTS;
Keywords:
agouti related protein; minimized human agouti related protein; nuclear magnetic resonance structure; total chemical synthesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Millhauser, GL Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA Univ Calif Santa Cruz Santa Cruz CA USA 95064 CA 95064 USA
Citazione:
K.A. Bolin et al., "NMR structure of a minimized human agouti related protein prepared by total chemical synthesis", FEBS LETTER, 451(2), 1999, pp. 125-131

Abstract

The structure of the chemically synthesized C-terminal region of the humanagouti related protein (AGRP) was determined by 2D H-1 NMR. Referred to asminimized agouti related protein, MARP is a 46 residue polypeptide containing 10 Cys residues involved in five disulfide bonds that retains the biological activity of full length AGRP, AGRP is a mammalian signaling molecule,involved in weight homeostasis, that causes adult onset obesity When overexpressed in mice. AGRP was originally identified by homology to the agouti protein, another potent signaling molecule involved in obesity disorders inmice. While AGRP's exact mechanism of action is unknown, it has been identified as a competitive antagonist of melanocortin receptors 3 and 4 (MC3r, MC4r), and MC4r in particular is implicated in the hypothalamic control of feeding behavior. Full length agouti and AGRP are only 25% homologous, however, their active C-terminal regions are similar to 40% homologous, With nine out of the 10 Cys residues spatially conserved. Until now, 3D structureshave not been available for either agouti, AGRP or their C-terminal regions. The NMR structure of MARP reported here can be characterized as three major loops, with four of the five disulfide bridges at the base of the structure, Though its fold is well defined, no canonical secondary structure is identified. While previously reported structural models of the C-terminal region of AGRP Were attempted based on Cys homology between AGRP and certaintoxin proteins, we find that Cys spacing is not sufficient to correctly determine the 3D fold of the molecule, (C) 1999 Federation of European Biochemical Societies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 18:42:49