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1gzr

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Revision as of 10:47, 5 November 2007 by OCA (Talk | contribs)
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1gzr, resolution 2.00Å

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HUMAN INSULIN-LIKE GROWTH FACTOR; ESRF DATA

Overview

Human insulin-like growth factors I and II (hIGF-I, hIGF-II) are potent, stimulators of cell and growth processes. They display high sequence, similarity to both the A and B chains of insulin but contain an additional, connecting C-domain, which reflects their secretion without specific, packaging or precursor conversion. IGFs also have an extension at the, C-terminus known as the D-domain. This paper describes four homologous, hIGF-1 structures, obtained from crystals grown in the presence of the, detergent SB12, which reveal additional detail in the C- and D-domains., Two different detergent binding modes observed in the crystals may reflect, different hIGF-I biological properties such as the interaction with IGF, binding proteins and self-aggregation. While the helical core of hIGF-I is, very similar to that in insulin, there are distinct differences in the, region of hIGF-I corresponding to the insulin B chain C-terminus, residues, B25-B30. In hIGF-I, these residues (24-29) and the following C-domain form, an extensive loop protruding 20 A from the core, which results in a, substantially different conformation for the receptor binding epitope in, hIGF-I compared to insulin. One notable feature of the structures, presented here is demonstration of peptide-bond cleavage between Ser35 and, Arg36 resulting in an apparent gap between residues 35 and 39. The, equivalent region of proinsulin is involved in hormone processing, demanding a reassessment of the structural integrity of hIGF-I in relation, to its biological function.

About this Structure

1GZR is a Single protein structure of sequence from Homo sapiens with C15 as ligand. Structure known Active Site: C15. Full crystallographic information is available from OCA.

Reference

Structural origins of the functional divergence of human insulin-like growth factor-I and insulin., Brzozowski AM, Dodson EJ, Dodson GG, Murshudov GN, Verma C, Turkenburg JP, de Bree FM, Dauter Z, Biochemistry. 2002 Jul 30;41(30):9389-97. PMID:12135360

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