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PDBsum entry 2iwi
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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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Crystal structure of the human pim2 in complex with a ruthenium organometallic ligand ru1
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Structure:
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Serine/threonine-protein kinase pim-2. Chain: a, b. Synonym: human pim2, pim-2h. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: star.
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Biol. unit:
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Monomer (from PDB file)
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Resolution:
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2.80Å
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R-factor:
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0.244
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R-free:
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0.289
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Authors:
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S.Russo,J.E.Debreczeni,A.Amos,A.N.Bullock,O.Fedorov,F.Niesen, F.Sobott,A.Turnbull,A.C.W.Pike,E.Ugochukwu,E.Papagrigoriou, G.Bunkoczi,F.Gorrec,A.Edwards,C.Arrowsmith,J.Weigelt,M.Sundstrom, F.Von Delft,S.Knapp
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Key ref:
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A.N.Bullock
et al.
(2009).
Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor.
Plos One,
4,
e7112.
PubMed id:
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Date:
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30-Jun-06
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Release date:
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02-Aug-06
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PROCHECK
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Headers
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References
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Q9P1W9
(PIM2_HUMAN) -
Serine/threonine-protein kinase pim-2 from Homo sapiens
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Seq:
Struc:
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311 a.a.
244 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.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[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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Plos One
4:e7112
(2009)
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PubMed id:
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Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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G.E.Atilla-Gokcumen,
L.Di Costanzo,
and
E.Meggers
(2011).
Structure of anticancer ruthenium half-sandwich complex bound to glycogen synthase kinase 3β.
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J Biol Inorg Chem,
16,
45-50.
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PDB code:
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A.Casini,
C.Temperini,
C.Gabbiani,
C.T.Supuran,
and
L.Messori
(2010).
The x-ray structure of the adduct between NAMI-A and carbonic anhydrase provides insights into the reactivity of this metallodrug with proteins.
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ChemMedChem,
5,
1989-1994.
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PDB code:
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L.Brault,
C.Gasser,
F.Bracher,
K.Huber,
S.Knapp,
and
J.Schwaller
(2010).
PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers.
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Haematologica,
95,
1004-1015.
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P.Heffeter,
K.Böck,
B.Atil,
M.A.Reza Hoda,
W.Körner,
C.Bartel,
U.Jungwirth,
B.K.Keppler,
M.Micksche,
W.Berger,
and
G.Koellensperger
(2010).
Intracellular protein binding patterns of the anticancer ruthenium drugs KP1019 and KP1339.
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J Biol Inorg Chem,
15,
737-748.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
