1m7n

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spinqualitylabelsall models 1m7n, resolution 2.7Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Unactivated APO Insulin-like Growth Factor-1 Receptor Kinase Domain

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The x-ray structure of the unactivated kinase domain of insulin-like, growth factor-1 receptor (IGFRK-0P) is reported here at 2.7 A resolution., IGFRK-0P is composed of two lobes connected by a hinge region. The, N-terminal lobe of the kinase is a twisted beta-sheet flanked by a single, helix, and the C-terminal lobe comprises eight alpha-helices and four, short beta-strands. The ATP binding pocket and the catalytic center reside, at the interface of the two lobes. Despite the overall similarity to other, receptor tyrosine kinases, three notable conformational modifications are, observed: 1) this kinase adopts a more closed structure, with its two, lobes rotated further toward each other; 2) the conformation of the, proximal end of the activation loop (residues 1121-1129) is different; 3), the orientation of the nucleotide-binding loop is altered. Collectively, these alterations lead to a different ATP-binding pocket that might impact, on inhibitor designs for IGFRK-0P. Two molecules of IGFRK-0P are seen in, the asymmetric unit; they are associated as a dimer with their ATP binding, clefts facing each other. The ordered N terminus of one monomer approaches, the active site of the other, suggesting that the juxtamembrane region of, one molecule could come into close proximity to the active site of the, other.

Disease

Known disease associated with this structure: Intrauterine and postnatal growth retardation OMIM:[147370]

About this Structure

1M7N is a Single protein structure of sequence from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity., Munshi S, Kornienko M, Hall DL, Reid JC, Waxman L, Stirdivant SM, Darke PL, Kuo LC, J Biol Chem. 2002 Oct 11;277(41):38797-802. Epub 2002 Jul 22. PMID:12138114

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