SandboxPKA

IntroductionIntroduction

spinqualitylabelsall models ABL1 homo-dimer complex Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

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(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

spinqualitylabelsall models c-Abl tyrosine kinase Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

spinqualitylabelsall models Catalitic domain Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image