2hr7

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(New page: 200px<br /> <applet load="2hr7" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hr7, resolution 2.320&Aring;" /> '''Insulin receptor (...)
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<applet load="2hr7" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="2hr7, resolution 2.32&Aring;" />
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'''Insulin receptor (domains 1-3)'''<br />
'''Insulin receptor (domains 1-3)'''<br />
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==Disease==
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==Overview==
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Known diseases associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Leprechaunism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Rabson-Mendenhall syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]]
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The insulin receptor (IR) and the type-1 insulin-like growth factor, receptor (IGF1R) are homologous multidomain proteins that bind insulin and, IGF with differing specificity. Here we report the crystal structure of, the first three domains (L1-CR-L2) of human IR at 2.3 A resolution and, compare it with the previously determined structure of the corresponding, fragment of IGF1R. The most important differences seen between the two, receptors are in the two regions governing ligand specificity. The first, is at the corner of the ligand-binding surface of the L1 domain, where the, side chain of F39 in IR forms part of the ligand binding surface involving, the second (central) beta-sheet. This is very different to the location of, its counterpart in IGF1R, S35, which is not involved in ligand binding., The second major difference is in the sixth module of the CR domain, where, IR contains a larger loop that protrudes further into the ligand-binding, pocket. This module, which governs IGF1-binding specificity, shows, negligible sequence identity, significantly more alpha-helix, an, additional disulfide bond, and opposite electrostatic potential compared, to that of the IGF1R.
==About this Structure==
==About this Structure==
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2HR7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, SO4, P33 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HR7 OCA].
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2HR7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=P33:'>P33</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HR7 OCA].
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==Reference==
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The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity., Lou M, Garrett TP, McKern NM, Hoyne PA, Epa VC, Bentley JD, Lovrecz GO, Cosgrove LJ, Frenkel MJ, Ward CW, Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12429-34. Epub 2006 Aug 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16894147 16894147]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: hormone receptor]]
[[Category: hormone receptor]]
[[Category: leucine rich repeat]]
[[Category: leucine rich repeat]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:35:17 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:22:11 2008''

Revision as of 09:22, 23 January 2008


2hr7, resolution 2.32Å

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Insulin receptor (domains 1-3)

Overview

The insulin receptor (IR) and the type-1 insulin-like growth factor, receptor (IGF1R) are homologous multidomain proteins that bind insulin and, IGF with differing specificity. Here we report the crystal structure of, the first three domains (L1-CR-L2) of human IR at 2.3 A resolution and, compare it with the previously determined structure of the corresponding, fragment of IGF1R. The most important differences seen between the two, receptors are in the two regions governing ligand specificity. The first, is at the corner of the ligand-binding surface of the L1 domain, where the, side chain of F39 in IR forms part of the ligand binding surface involving, the second (central) beta-sheet. This is very different to the location of, its counterpart in IGF1R, S35, which is not involved in ligand binding., The second major difference is in the sixth module of the CR domain, where, IR contains a larger loop that protrudes further into the ligand-binding, pocket. This module, which governs IGF1-binding specificity, shows, negligible sequence identity, significantly more alpha-helix, an, additional disulfide bond, and opposite electrostatic potential compared, to that of the IGF1R.

About this Structure

2HR7 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. 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

The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity., Lou M, Garrett TP, McKern NM, Hoyne PA, Epa VC, Bentley JD, Lovrecz GO, Cosgrove LJ, Frenkel MJ, Ward CW, Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12429-34. Epub 2006 Aug 7. PMID:16894147

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