SandboxPKA
From Proteopedia
| Line 39: | Line 39: | ||
- '''Tyrosine specific kinases''': c-Abl is included in this group | - '''Tyrosine specific kinases''': c-Abl is included in this group | ||
| - | <ref>Leukemia research 34 (10): 1255–1268. doi:10.1016/j.leukres.2010.04.016. PMID 2053738<ref> | + | <ref>Leukemia research 34 (10): 1255–1268. doi:10.1016/j.leukres.2010.04.016. PMID 2053738</ref> |
| Line 69: | Line 69: | ||
It is responsible of both, ATP binding as well as protein binding. | It is responsible of both, ATP binding as well as protein binding. | ||
| - | <StructureSection load='3DY7' size='350' side='right' caption='Catalitic domain' scene='SandboxPKA/Catalitic_core_1/1'> | ||
| - | The crystal structure of the catalytic domain of Abl was reported by Schindler et. al in 2000 | + | ==Your Heading Here (maybe something like 'Structure')==<StructureSection load='3DY7' size='300' side='right' caption='Catalytic Domain (PDB entry [[3DY7]])' scene='SandboxPKA/Catalitic_core_1/1'>The crystal structure of the catalytic domain of Abl was reported by Schindler et. al in 2000. The binding of STI-571 promotes the adoption by the kinase of an inactive conformation in which a centrally located "activation loop" is not phosphorylated. |
Catalitic subunit of c-Abl protein is composed by two different regions: | Catalitic subunit of c-Abl protein is composed by two different regions: | ||
• ATP-binding pocket: is mainly mediated by alfa-helix | • ATP-binding pocket: is mainly mediated by alfa-helix | ||
| - | • Protein-binding pocket: lamina-B domain | + | • Protein-binding pocket: lamina-B domain</StructureSection> |
| + | |||
| - | </StructureSection> | ||
== Resistance == | == Resistance == | ||
Revision as of 16:14, 5 December 2012
Contents |
Introduction
|
The c-Abl protein 1 (ABL1), also known as Abelson kinase, is a non-receptor tyrosine kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. [1] [2] Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. In more than 90% cases, chronic myelogeneous leukemia (CML) is caused by chromosomal abnormality resulting in the formation the Philadelphia chromosome. This chromosome is formed by fusion between Abelson (Abl) tyrosine kinase gene at chromosome 9 and break point cluster (Bcr) gene at chromosome 22, resulting in the chimeric oncogene Bcr-Abl and a constitutively active Bcr-Abl tyrosine kinase. Small molecule inhibitors of Bcr-Abl that bind to the kinase domain can be used to treat CML [3]
Reaction
Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal) phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting side protein function.
The enzymes are classified into two broad groups, characterised with respect to substrate specificity:
- Serine/threonine kinases
- Tyrosine specific kinases: c-Abl is included in this group [4]
</StructureSection>
Structure
All of the protein kinases have a similar bilobal fold, and their key structural features have been well studied
| |||||||||||
Catalytic domain
It is responsible of both, ATP binding as well as protein binding.
| |||||||||||
Resistance
References
- ↑ http://www.ncbi.nlm.nih.gov/pubmed/9037071
- ↑ http://www.ncbi.nlm.nih.gov/pubmed/11114745
- ↑ Crystal Structures of the Kinase Domain of c-Abl in Complex with the Small Molecule Inhibitors PD173955 and STI571
- ↑ Leukemia research 34 (10): 1255–1268. doi:10.1016/j.leukres.2010.04.016. PMID 2053738
