1mr0

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===SOLUTION NMR STRUCTURE OF AGRP(87-120; C105A)===
===SOLUTION NMR STRUCTURE OF AGRP(87-120; C105A)===
{{ABSTRACT_PUBMED_12056887}}
{{ABSTRACT_PUBMED_12056887}}
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==Disease==
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[[http://www.uniprot.org/uniprot/AGRP_HUMAN AGRP_HUMAN]] Genetic variations in AGRP may be a cause of obesity (OBESITY) [MIM:[http://omim.org/entry/601665 601665]]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:12213871</ref>
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==Function==
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[[http://www.uniprot.org/uniprot/AGRP_HUMAN AGRP_HUMAN]] Plays a role in weight homeostasis. Involved in the control of feeding behavior through the central melanocortin system. Acts as alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP production mediated by stimulation of melanocortin receptors within the hypothalamus and adrenal gland. Has very low activity with MC5R (By similarity). Is an inverse agonist for MC3R and MC4R being able to suppress their constitutive activity. It promotes MC3R and MC4R endocytosis in an arrestin-dependent manner.<ref>PMID:9892020</ref><ref>PMID:11145747</ref><ref>PMID:17041250</ref><ref>PMID:10371151</ref><ref>PMID:15927146</ref>
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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<ref group="xtra">PMID:012056887</ref><references group="xtra"/>
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<ref group="xtra">PMID:012056887</ref><references group="xtra"/><references/>
[[Category: Barsh, G S.]]
[[Category: Barsh, G S.]]
[[Category: Chai, B.]]
[[Category: Chai, B.]]

Revision as of 20:32, 24 March 2013

Template:STRUCTURE 1mr0

Contents

SOLUTION NMR STRUCTURE OF AGRP(87-120; C105A)

Template:ABSTRACT PUBMED 12056887

Disease

[AGRP_HUMAN] Genetic variations in AGRP may be a cause of obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.[1]

Function

[AGRP_HUMAN] Plays a role in weight homeostasis. Involved in the control of feeding behavior through the central melanocortin system. Acts as alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP production mediated by stimulation of melanocortin receptors within the hypothalamus and adrenal gland. Has very low activity with MC5R (By similarity). Is an inverse agonist for MC3R and MC4R being able to suppress their constitutive activity. It promotes MC3R and MC4R endocytosis in an arrestin-dependent manner.[2][3][4][5][6]

About this Structure

1mr0 is a 1 chain structure. This structure supersedes the now removed PDB entry 1mc6. Full experimental information is available from OCA.

Reference

  • Jackson PJ, McNulty JC, Yang YK, Thompson DA, Chai B, Gantz I, Barsh GS, Millhauser GL. Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity. Biochemistry. 2002 Jun 18;41(24):7565-72. PMID:12056887
  1. ↑ Argyropoulos G, Rankinen T, Neufeld DR, Rice T, Province MA, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. A polymorphism in the human agouti-related protein is associated with late-onset obesity. J Clin Endocrinol Metab. 2002 Sep;87(9):4198-202. PMID:12213871
  2. ↑ Yang YK, Thompson DA, Dickinson CJ, Wilken J, Barsh GS, Kent SB, Gantz I. Characterization of Agouti-related protein binding to melanocortin receptors. Mol Endocrinol. 1999 Jan;13(1):148-55. PMID:9892020
  3. ↑ Nijenhuis WA, Oosterom J, Adan RA. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol. 2001 Jan;15(1):164-71. PMID:11145747
  4. ↑ Breit A, Wolff K, Kalwa H, Jarry H, Buch T, Gudermann T. The natural inverse agonist agouti-related protein induces arrestin-mediated endocytosis of melanocortin-3 and -4 receptors. J Biol Chem. 2006 Dec 8;281(49):37447-56. Epub 2006 Oct 14. PMID:17041250 doi:10.1074/jbc.M605982200
  5. ↑ Bolin KA, Anderson DJ, Trulson JA, Thompson DA, Wilken J, Kent SB, Gantz I, Millhauser GL. NMR structure of a minimized human agouti related protein prepared by total chemical synthesis. FEBS Lett. 1999 May 21;451(2):125-31. PMID:10371151
  6. ↑ de Rijke CE, Jackson PJ, Garner KM, van Rozen RJ, Douglas NR, Kas MJ, Millhauser GL, Adan RA. Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. Biochem Pharmacol. 2005 Jul 15;70(2):308-16. PMID:15927146 doi:10.1016/j.bcp.2005.04.033

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