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PDBsum entry 2xyn
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Human abl2 in complex with aurora kinase inhibitor vx-680
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Structure:
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Tyrosine-protein kinase abl2. Chain: a, b, c. Fragment: residues 243-510. Synonym: abelson murine leukemia viral oncogene homolog 2, abelson- related gene protein, tyrosine-protein kinase arg, abl2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.
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Resolution:
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2.81Å
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R-factor:
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0.248
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R-free:
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0.284
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Authors:
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E.Salah,E.Ugochukwu,J.M.Elkins,A.J.Barr,B.Shrestha,P.Savitsky, P.Mahajan,J.R.C.Muniz,W.W.Yue,A.Chaikuad,F.Von Delft,C.Bountra, C.H.Arrowsmith,J.Weigelt,A.Edwards,S.Knapp,Structural Genomics Consortium (Sgc)
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Key ref:
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E.Salah
et al.
(2011).
Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class.
J Med Chem,
54,
2359-2367.
PubMed id:
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Date:
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18-Nov-10
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Release date:
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01-Dec-10
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Supersedes:
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PROCHECK
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Headers
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References
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P42684
(ABL2_HUMAN) -
Tyrosine-protein kinase ABL2 from Homo sapiens
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Seq:
Struc:
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1182 a.a.
264 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.10.2
- non-specific protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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J Med Chem
54:2359-2367
(2011)
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PubMed id:
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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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E.Salah,
E.Ugochukwu,
A.J.Barr,
F.von Delft,
S.Knapp,
J.M.Elkins.
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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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Links
