2fo0

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[[Image:2fo0.gif|left|200px]]<br /><applet load="2fo0" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2fo0.gif|left|200px]]
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caption="2fo0, resolution 2.27&Aring;" />
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'''Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase'''<br />
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{{Structure
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|PDB= 2fo0 |SIZE=350|CAPTION= <scene name='initialview01'>2fo0</scene>, resolution 2.27&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=P16:6-(2,6-DICHLOROPHENYL)-2-{[3-(HYDROXYMETHYL)PHENYL]AMINO}-8-METHYLPYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>P16</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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|ACTIVITY= [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]
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|GENE= c-Abl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2FO0 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=MYR:'>MYR</scene>, <scene name='pdbligand=P16:'>P16</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=2FO0 OCA].
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2FO0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FO0 OCA].
==Reference==
==Reference==
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Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase., Nagar B, Hantschel O, Seeliger M, Davies JM, Weis WI, Superti-Furga G, Kuriyan J, Mol Cell. 2006 Mar 17;21(6):787-98. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16543148 16543148]
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Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase., Nagar B, Hantschel O, Seeliger M, Davies JM, Weis WI, Superti-Furga G, Kuriyan J, Mol Cell. 2006 Mar 17;21(6):787-98. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16543148 16543148]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: sh3-sh2 clamp]]
[[Category: sh3-sh2 clamp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:21 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:54:45 2008''

Revision as of 14:54, 20 March 2008

Image:2fo0.gif


PDB ID 2fo0

Drag the structure with the mouse to rotate
, resolution 2.27Å
Ligands: , and
Gene: c-Abl (Homo sapiens)
Activity: Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2
Coordinates: save as pdb, mmCIF, xml



Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase


Contents

Overview

The tyrosine kinase c-Abl is inactivated by interactions made by its SH3 and SH2 domains with the distal surface of the kinase domain. We present a crystal structure of a fragment of c-Abl which reveals that a critical N-terminal cap segment, not visualized in previous structures, buttresses the SH3-SH2 substructure in the autoinhibited state and locks it onto the distal surface of the kinase domain. Surprisingly, the N-terminal cap is phosphorylated on a serine residue that interacts with the connector between the SH3 and SH2 domains. Small-angle X-ray scattering (SAXS) analysis shows that a mutated form of c-Abl, in which the N-terminal cap and two other key contacts in the autoinhibited state are deleted, exists in an extended array of the SH3, SH2, and kinase domains. This alternative conformation of Abl is likely to prolong the active state of the kinase by preventing it from returning to the autoinhibited state.

Disease

Known diseases associated with this structure: Leukemia, Philadelphia chromosome-positive, resistant to imatinib OMIM:[189980]

About this Structure

2FO0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase., Nagar B, Hantschel O, Seeliger M, Davies JM, Weis WI, Superti-Furga G, Kuriyan J, Mol Cell. 2006 Mar 17;21(6):787-98. PMID:16543148

Page seeded by OCA on Thu Mar 20 16:54:45 2008

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