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1cq0

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1cq0

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SOLUTION STRUCTURE OF A HUMAN HYPOCRETIN-2/OREXIN-B'SOLUTION STRUCTURE OF A HUMAN HYPOCRETIN-2/OREXIN-B '

Contents

Overview

Orexin-A and orexin-B (also called hypocretin-1 and hypocretin-2, respectively) are novel hypothalamic neuropeptides encoded by a single mRNA transcript; they stimulate food intake. We have determined the three-dimensional solution structure of human hypocretin-2/orexin-B using two-dimensional 1H-NMR data and dynamical simulated annealing calculations. On the basis of NOEs, 3JHNalpha coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin-2/orexin-B was deduced to consist of two alpha-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80 degrees relative to helix II. Hybrid distance geometry and simulated-annealing protocols were used to generate an ensemble of 30 structures with no constraint violations greater than 0.03 nm for distances and 3 degrees for angles. In addition, human hypocretin-2/orexin-B shares a similar secondary-structural motif with human neuropeptide Y. This result can form the basis for further study on ligand-receptor recognition of human orexin receptors.

Disease

Known diseases associated with this structure: Narcolepsy OMIM:[602358], Porphyria variegata OMIM:[600923]

About this Structure

1CQ0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B., Lee JH, Bang E, Chae KJ, Kim JY, Lee DW, Lee W, Eur J Biochem. 1999 Dec;266(3):831-9. PMID:10583376

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