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PDBsum entry 4otg
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Transferase/transferase inhibitor
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PDB id
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4otg
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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 prk1 in complex with the clinical compounds lestaurtinib and tofacitinib reveal ligand induced conformational changes.
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Authors
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P.Chamberlain,
S.Delker,
B.Pagarigan,
A.Mahmoudi,
P.Jackson,
M.Abbasian,
J.Muir,
N.Raheja,
B.Cathers.
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Ref.
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Plos One, 2014,
9,
e103638.
[DOI no: ]
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PubMed id
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Abstract
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Protein kinase C related kinase 1 (PRK1) is a component of Rho-GTPase, androgen
receptor, histone demethylase and histone deacetylase signaling pathways
implicated in prostate and ovarian cancer. Herein we describe the crystal
structure of PRK1 in apo form, and also in complex with a panel of literature
inhibitors including the clinical candidates lestaurtinib and tofacitinib, as
well as the staurosporine analog Ro-31-8220. PRK1 is a member of the AGC-kinase
class, and as such exhibits the characteristic regulatory sequence at the
C-terminus of the catalytic domain - the 'C-tail'. The C-tail fully encircles
the catalytic domain placing a phenylalanine in the ATP-binding site. Our
inhibitor structures include examples of molecules which both interact with, and
displace the C-tail from the active site. This information may assist in the
design of inhibitors targeting both PRK and other members of the AGC kinase
family.
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