2myo

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(New page: 200px<br /><applet load="2myo" size="450" color="white" frame="true" align="right" spinBox="true" caption="2myo" /> '''SOLUTION STRUCTURE OF MYOTROPHIN, NMR, MINIM...)
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Revision as of 10:39, 21 November 2007


2myo

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SOLUTION STRUCTURE OF MYOTROPHIN, NMR, MINIMIZED AVERAGE STRUCTURE

Overview

BACKGROUND: Myotrophin is a 12.5 kDa protein that appears to have a key, role in the initiation of cardiac hypertrophy, a central process in many, heart diseases. Myotrophin primarily comprises ankyrin-like (ANK) repeats, the 33 amino acid motifs involved in a wide range of protein-protein, interactions. As a first step in the structure-based search for cardiac, hypertrophy antagonists and in order to gain insight into the molecular, basis of action of the ubiquitous and multifunctional ANK repeat motif, we, have determined the solution structure of myotrophin using, multidimensional heteronuclear NMR spectroscopy. RESULTS: The myotrophin, structure determination was based on 2786 experimental NMR restraints, and, the precision of the coordinates for the final 45 simulated-annealing, structures is 0.43 A for the backbone atoms and 0.87 A for all atoms. The, structure of myotrophin is well defined and is ellipsoidal: approximately, 46 A long and 21 A wide. The ANK repeats, which constitute the main part, of the myotrophin structure, are characteristic of a hairpin-like, protruding tip followed by a helix-turn-helix motif. The V-shaped, helix-turn-helix of the ANK repeats stack sequentially in bundles and are, stabilized by compact hydrophobic cores, whereas the protruding tips are, less ordered. This arrangement is quite different to the continuous, beta-sheet topology observed in the corresponding regions of another ANK, protein, 53BP2, the structure of which was determined in complex with p53., CONCLUSIONS: The solution structure of myotrophin provides important, insights into the structural and dynamic features of the ANK motif, and, suggests that the protruding tips with highly variable sequences may be, critical to facilitate diverse protein-protein recognition. The present, structure also provides a molecular basis for the further functional, characterization of myotrophin and the development of therapeutics for, hypertrophy-related heart diseases.

About this Structure

2MYO is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

The structural basis of ankyrin-like repeat function as revealed by the solution structure of myotrophin., Yang Y, Nanduri S, Sen S, Qin J, Structure. 1998 May 15;6(5):619-26. PMID:9634699

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