1MR0

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

「1MC6」から置き換えられました

1MR0 の概要

• エントリーDOI: 10.2210/pdb1mr0/pdb
• 関連するPDBエントリー: 1HYK 1MC6
• 分子名称: AGOUTI RELATED PROTEIN (1 entity in total)
• 機能のキーワード: rational protein design, ick, inhibitor cystine knot, agrp, agouti-related protein, melanocortin, signaling protein
• 細胞内の位置: Secreted: O00253
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3912.59

構造登録者

Jackson, P.J.,Mcnulty, J.C.,Yang, Y.K.,Thompson, D.A.,Chai, B.,Gantz, I.,Barsh, G.S.,Millhauser, G.M. (登録日: 2002-09-17, 公開日: 2002-10-02, 最終更新日: 2024-10-09)

主引用文献

Jackson, P.J.,McNulty, J.C.,Yang, Y.K.,Thompson, D.A.,Chai, B.,Gantz, I.,Barsh, G.S.,Millhauser, G.L.
Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity.
Biochemistry, 41:7565-7572, 2002

PubMed Abstract: 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.

PubMed: 12056887
DOI: 10.1021/bi012000x

実験手法

SOLUTION NMR