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PDBsum entry 2xyn
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References listed in PDB file
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Key reference
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Title
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Crystal structures of abl-Related gene (abl2) in complex with imatinib, Tozasertib (vx-680), And a type i inhibitor of the triazole carbothioamide class.
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Authors
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E.Salah,
E.Ugochukwu,
A.J.Barr,
F.Von delft,
S.Knapp,
J.M.Elkins.
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Ref.
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J Med Chem, 2011,
54,
2359-2367.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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ABL2 (also known as ARG (ABL related gene)) is closely related to the
well-studied Abelson kinase cABL. ABL2 is involved in human neoplastic diseases
and is deregulated in solid tumors. Oncogenic gene translocations occur in acute
leukemia. So far no structural information for ABL2 has been reported. To
elucidate structural determinants for inhibitor interaction, we determined the
cocrystal structure of ABL2 with the oncology drug imatinib. Interestingly,
imatinib not only interacted with the ATP binding site of the inactive kinase
but was also bound to the regulatory myristate binding site. This structure may
therefore serve as a tool for the development of allosteric ABL inhibitors. In
addition, we determined the structures of ABL2 in complex with VX-680 and with
an ATP-mimetic type I inhibitor, which revealed an interesting position of the
DFG motif intermediate between active and inactive conformations, that may also
serve as a template for future inhibitor design.
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