1mr0
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(New page: 200px<br /> <applet load="1mr0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mr0" /> '''SOLUTION NMR STRUCTURE OF AGRP(87-120; C105...)
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Revision as of 16:07, 12 November 2007
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SOLUTION NMR STRUCTURE OF AGRP(87-120; C105A)
Contents |
Overview
The agouti-related protein (AGRP) is an endogenous antagonist of the, melanocortin receptors MC3R and MC4R found in the hypothalamus and, exhibits potent orexigenic activity. The cysteine-rich C-terminal domain, of this protein, corresponding to AGRP(87-132), exhibits receptor binding, affinity and antagonism equivalent to that of the full-length protein. The, NMR structure of this active domain was recently determined and suggested, that melanocortin receptor contacts were made primarily by two loops, presented by a well-structured cystine knot domain within AGRP(87-132), [McNulty et al. (2001) Biochemistry 40, 15520-15527]. This hypothesis is, tested here with NMR structure and activity studies of a 34-residue AGRP, analogue designed to contain only the cystine knot domain. The designed, miniprotein folds to a homogeneous product, retains the desired cystine, knot architecture, functions as an antagonist, and maintains the, melanocortin receptor pharmacological profile of AGRP(87-132). The, AGRP-like activity of this molecule supports the hypothesis that indeed, the cystine knot region possesses the melanocortin receptor contact, points. Moreover, this potent AGRP analogue is synthetically accessible, may serve in the development of therapeutics for the treatment of diseases, related to energy balance. and may also find use as a new reagent for, probing melanocortin receptor structure and function.
Disease
Known diseases associated with this structure: Leanness, inherited OMIM:[602311], Obesity, late-onset OMIM:[602311]
About this Structure
1MR0 is a Single protein structure of sequence from [1]. This structure superseeds the now removed PDB entry 1MC6. Full crystallographic information is available from OCA.
Reference
Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity., Jackson PJ, McNulty JC, Yang YK, Thompson DA, Chai B, Gantz I, Barsh GS, Millhauser GL, Biochemistry. 2002 Jun 18;41(24):7565-72. PMID:12056887
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