SandboxPKA: Difference between revisions

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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.
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.
http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetImage.pl?kegg_id=D08646


The enzymes are classified into two broad groups, characterised with respect to substrate specificity:  
The enzymes are classified into two broad groups, characterised with respect to substrate specificity:  
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- '''Serine/threonine kinases'''  
- '''Serine/threonine kinases'''  
- '''Tyrosine specific kinases''': c-Abl is included in this group
- '''Tyrosine specific kinases''': c-Abl is included in this group
[[Image:reaction.jpg]]


(Leukemia research 34 (10): 1255–1268. doi:10.1016/j.leukres.2010.04.016. PMID 2053738)
(Leukemia research 34 (10): 1255–1268. doi:10.1016/j.leukres.2010.04.016. PMID 2053738)

Revision as of 01:24, 5 December 2012

IntroductionIntroduction

ABL1 homo-dimer complex

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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. 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 of a so-called Philadelphia chromosome. It is caused 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.

ReactionReaction

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

(Leukemia research 34 (10): 1255–1268. doi:10.1016/j.leukres.2010.04.016. PMID 2053738)

StructureStructure

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Morado dominio SH3

Rojo dominio SH2


c-Abl tyrosine kinase

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Catalytic domainCatalytic domain

It is responsible of both, ATP binding as well as protein binding.


Catalitic subunit of c-Abl protein is composed by two different regions: • ATP-binding pocket: is mainly mediated by alfa-helix • Protein-binding pocket: lamina-B domain


Catalitic domain

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Cristina Murga, Joel L. Sussman