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PDBsum entry 2iwi
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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 structure of the pim2 kinase in complex with an organoruthenium inhibitor.
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Authors
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A.N.Bullock,
S.Russo,
A.Amos,
N.Pagano,
H.Bregman,
J.E.Debreczeni,
W.H.Lee,
F.Von delft,
E.Meggers,
S.Knapp.
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Ref.
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Plos One, 2009,
4,
e7112.
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PubMed id
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Abstract
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BACKGROUND: The serine/threonine kinase PIM2 is highly expressed in human
leukemia and lymphomas and has been shown to positively regulate survival and
proliferation of tumor cells. Its diverse ATP site makes PIM2 a promising target
for the development of anticancer agents. To date our knowledge of catalytic
domain structures of the PIM kinase family is limited to PIM1 which has been
extensively studied and which shares about 50% sequence identity with PIM2.
PRINCIPAL FINDINGS: Here we determined the crystal structure of PIM2 in complex
with an organoruthenium complex (inhibition in sub-nanomolar level). Due to its
extraordinary shape complementarity this stable organometallic compound is a
highly potent inhibitor of PIM kinases. SIGNIFICANCE: The structure of PIM2
revealed several differences to PIM1 which may be explored further to generate
isoform selective inhibitors. It has also demonstrated how an organometallic
inhibitor can be adapted to the binding site of protein kinases to generate
highly potent inhibitors. ENHANCED VERSION: This article can also be viewed as
an enhanced version in which the text of the article is integrated with
interactive 3D representations and animated transitions. Please note that a web
plugin is required to access this enhanced functionality. Instructions for the
installation and use of the web plugin are available in Text S1.
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