2fo0
From Proteopedia
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|PDB= 2fo0 |SIZE=350|CAPTION= <scene name='initialview01'>2fo0</scene>, resolution 2.27Å | |PDB= 2fo0 |SIZE=350|CAPTION= <scene name='initialview01'>2fo0</scene>, resolution 2.27Å | ||
|SITE= | |SITE= | ||
| - | |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> | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene> |
| - | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= c-Abl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= c-Abl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fo0 OCA], [http://www.ebi.ac.uk/pdbsum/2fo0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fo0 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=189980 189980]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Superti-Furga, G.]] | [[Category: Superti-Furga, G.]] | ||
[[Category: Weis, W I.]] | [[Category: Weis, W I.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: MYR]] | ||
| - | [[Category: P16]] | ||
[[Category: autoinhibition]] | [[Category: autoinhibition]] | ||
[[Category: myristoylation]] | [[Category: myristoylation]] | ||
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[[Category: sh3-sh2 clamp]] | [[Category: sh3-sh2 clamp]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:05:29 2008'' |
Revision as of 00:05, 31 March 2008
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| , resolution 2.27Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | c-Abl (Homo sapiens) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase
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.
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 Mon Mar 31 03:05:29 2008
