1opj
From Proteopedia
(New page: 200px<br /><applet load="1opj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1opj, resolution 1.75Å" /> '''Structural basis for...) |
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| - | [[Image:1opj.gif|left|200px]]<br /><applet load="1opj" size=" | + | [[Image:1opj.gif|left|200px]]<br /><applet load="1opj" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1opj, resolution 1.75Å" /> | caption="1opj, resolution 1.75Å" /> | ||
'''Structural basis for the auto-inhibition of c-Abl tyrosine kinase'''<br /> | '''Structural basis for the auto-inhibition of c-Abl tyrosine kinase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | c-Abl is normally regulated by an autoinhibitory mechanism, the disruption | + | c-Abl is normally regulated by an autoinhibitory mechanism, the disruption of which leads to chronic myelogenous leukemia. The details of this mechanism have been elusive because c-Abl lacks a phosphotyrosine residue that triggers the assembly of the autoinhibited form of the closely related Src kinases by internally engaging the SH2 domain. Crystal structures of c-Abl show that the N-terminal myristoyl modification of c-Abl 1b binds to the kinase domain and induces conformational changes that allow the SH2 and SH3 domains to dock onto it. Autoinhibited c-Abl forms an assembly that is strikingly similar to that of inactive Src kinases but with specific differences that explain the differential ability of the drug STI-571/Gleevec/imatinib (STI-571) to inhibit the catalytic activity of Abl, but not that of c-Src. |
==About this Structure== | ==About this Structure== | ||
| - | 1OPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CL, MYR and STI 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:// | + | 1OPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=MYR:'>MYR</scene> and <scene name='pdbligand=STI:'>STI</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=1OPJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Superti-Furga, G.]] | [[Category: Superti-Furga, G.]] | ||
[[Category: Veach, D.]] | [[Category: Veach, D.]] | ||
| - | [[Category: Young, M | + | [[Category: Young, M A.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: MYR]] | [[Category: MYR]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:20:11 2008'' |
Revision as of 12:20, 21 February 2008
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Structural basis for the auto-inhibition of c-Abl tyrosine kinase
Overview
c-Abl is normally regulated by an autoinhibitory mechanism, the disruption of which leads to chronic myelogenous leukemia. The details of this mechanism have been elusive because c-Abl lacks a phosphotyrosine residue that triggers the assembly of the autoinhibited form of the closely related Src kinases by internally engaging the SH2 domain. Crystal structures of c-Abl show that the N-terminal myristoyl modification of c-Abl 1b binds to the kinase domain and induces conformational changes that allow the SH2 and SH3 domains to dock onto it. Autoinhibited c-Abl forms an assembly that is strikingly similar to that of inactive Src kinases but with specific differences that explain the differential ability of the drug STI-571/Gleevec/imatinib (STI-571) to inhibit the catalytic activity of Abl, but not that of c-Src.
About this Structure
1OPJ is a Single protein structure of sequence from Mus musculus 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
Structural basis for the autoinhibition of c-Abl tyrosine kinase., Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, Clarkson B, Superti-Furga G, Kuriyan J, Cell. 2003 Mar 21;112(6):859-71. PMID:12654251
Page seeded by OCA on Thu Feb 21 14:20:11 2008
Categories: Mus musculus | Single protein | Transferase | Bornmann, W. | Clarkson, B. | Hantschel, O. | Kuriyan, J. | Nagar, B. | Scheffzek, K. | Superti-Furga, G. | Veach, D. | Young, M A. | CL | MYR | STI
