2fo0
From Proteopedia
(New page: 200px<br /> <applet load="2fo0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fo0, resolution 2.27Å" /> '''Organization of the...) |
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| - | [[Image:2fo0.gif|left|200px]]<br /> | + | [[Image:2fo0.gif|left|200px]]<br /><applet load="2fo0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fo0" size=" | + | |
caption="2fo0, resolution 2.27Å" /> | caption="2fo0, resolution 2.27Å" /> | ||
'''Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase'''<br /> | '''Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The tyrosine kinase c-Abl is inactivated by interactions made by its SH3 | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 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 MYR, P16 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:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Davies, J | + | [[Category: Davies, J M.]] |
[[Category: Hantschel, O.]] | [[Category: Hantschel, O.]] | ||
[[Category: Kuriyan, J.]] | [[Category: Kuriyan, J.]] | ||
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[[Category: Seeliger, M.]] | [[Category: Seeliger, M.]] | ||
[[Category: Superti-Furga, G.]] | [[Category: Superti-Furga, G.]] | ||
| - | [[Category: Weis, W | + | [[Category: Weis, W I.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: MYR]] | [[Category: MYR]] | ||
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[[Category: sh3-sh2 clamp]] | [[Category: sh3-sh2 clamp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:21 2008'' |
Revision as of 15:23, 21 February 2008
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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 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
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 Feb 21 17:23:21 2008
Categories: Homo sapiens | Single protein | Transferase | Davies, J M. | Hantschel, O. | Kuriyan, J. | Nagar, B. | Seeliger, M. | Superti-Furga, G. | Weis, W I. | GOL | MYR | P16 | Autoinhibition | Myristoylation | N-terminal cap | Phosphoserine | Sh3-sh2 clamp
