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PDBsum entry 1t45
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Transferase activator
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PDB id
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1t45
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* Residue conservation analysis
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PDB id:
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Transferase activator
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Title:
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Structural basis for the autoinhibition and sti-571 inhibition of c- kit tyrosine kinase
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Structure:
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Homo sapiens v-kit hardy-zuckerman 4 feline sarcoma viral oncogene homolog. Chain: a. Fragment: kit tyrosine kinase. Synonym: kit. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: kit. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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1.90Å
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R-factor:
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0.194
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R-free:
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0.222
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Authors:
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C.D.Mol,D.R.Dougan,T.R.Schneider,R.J.Skene,M.L.Kraus,D.N.Scheibe, G.P.Snell,H.Zou,B.C.Sang,K.P.Wilson
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Key ref:
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C.D.Mol
et al.
(2004).
Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
J Biol Chem,
279,
31655-31663.
PubMed id:
DOI:
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Date:
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28-Apr-04
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Release date:
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15-Jun-04
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PROCHECK
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Headers
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References
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P10721
(KIT_HUMAN) -
Mast/stem cell growth factor receptor Kit from Homo sapiens
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Seq:
Struc:
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976 a.a.
331 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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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.10.1
- receptor 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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DOI no:
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J Biol Chem
279:31655-31663
(2004)
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PubMed id:
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Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
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C.D.Mol,
D.R.Dougan,
T.R.Schneider,
R.J.Skene,
M.L.Kraus,
D.N.Scheibe,
G.P.Snell,
H.Zou,
B.C.Sang,
K.P.Wilson.
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ABSTRACT
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The activity of the c-Kit receptor protein-tyrosine kinase is tightly regulated
in normal cells, whereas deregulated c-Kit kinase activity is implicated in the
pathogenesis of human cancers. The c-Kit juxtamembrane region is known to have
an autoinhibitory function; however the precise mechanism by which c-Kit is
maintained in an autoinhibited state is not known. We report the 1.9-A
resolution crystal structure of native c-Kit kinase in an autoinhibited
conformation and compare it with active c-Kit kinase. Autoinhibited c-Kit is
stabilized by the juxtamembrane domain, which inserts into the kinase-active
site and disrupts formation of the activated structure. A 1.6-A crystal
structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates
that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in
an autoinhibited state. Together, these results provide a structural basis for
understanding c-Kit kinase autoinhibition and will facilitate the
structure-guided design of specific inhibitors that target the activated and
autoinhibited conformations of c-Kit kinase.
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Selected figure(s)
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Figure 4.
FIG. 4. The structure and environment surrounding the
frequently mutated residue Asp816 in the autoinhibited and
activated c-Kit kinase structures. A, view of the structural
environment surrounding Asp816 in the autoinhibited kinase
structure. Asp816 is situated between the P-loop and a short
region of 3[10] helix where the negatively charged Asp side
chain can stabilize the positively charged helical dipole. B,
view of the structural environment surrounding Asp816 in the
activated kinase structure. Arg815 and Ile^817 form  -sheet
hydrogen bonding interactions with Ile^79 and Asn787 of the
C-lobe to stabilize the activation loop in an extended
conformation.
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Figure 7.
FIG. 7. STI-571 binding and interactions with c-Kit kinase.
A, chemical structure of STI-571 and F[obs] - F[calc] omit
difference electron density calculated prior to building the
inhibitor into the co-crystal structure, contoured at 3  (blue)
and 6 (red). Key hydrogen
bonds are depicted. B, stereo view of STI-571 (purple) binding
to c-Kit showing key hydrogen bonds formed with the hinge
residue Cys673, gatekeeper residue Thr670, and conserved residue
Glu640. The polypeptide surrounding Trp557 from the virgin
autoinhibited c-Kit structure is shown superimposed on the
STI-571 complex structure.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
31655-31663)
copyright 2004.
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Figures were
selected
by the author.
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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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C.C.Smith,
Q.Wang,
C.S.Chin,
S.Salerno,
L.E.Damon,
M.J.Levis,
A.E.Perl,
K.J.Travers,
S.Wang,
J.P.Hunt,
P.P.Zarrinkar,
E.E.Schadt,
A.Kasarskis,
J.Kuriyan,
and
N.P.Shah
(2012).
Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia.
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Nature,
485,
260-263.
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C.L.Corless,
C.M.Barnett,
and
M.C.Heinrich
(2011).
Gastrointestinal stromal tumours: origin and molecular oncology.
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Nat Rev Cancer,
11,
865-878.
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K.Krasagakis,
I.Fragiadaki,
M.Metaxari,
S.Krüger-Krasagakis,
G.N.Tzanakakis,
E.N.Stathopoulos,
J.Eberle,
N.Tavernarakis,
and
A.D.Tosca
(2011).
KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro.
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J Cell Physiol,
226,
1099-1109.
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N.Jura,
X.Zhang,
N.F.Endres,
M.A.Seeliger,
T.Schindler,
and
J.Kuriyan
(2011).
Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms.
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Mol Cell,
42,
9.
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N.Singla,
H.Erdjument-Bromage,
J.P.Himanen,
T.W.Muir,
and
D.B.Nikolov
(2011).
A semisynthetic Eph receptor tyrosine kinase provides insight into ligand-induced kinase activation.
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Chem Biol,
18,
361-371.
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P.Dileo,
S.Pricl,
E.Tamborini,
T.Negri,
S.Stacchiotti,
A.Gronchi,
P.Posocco,
E.Laurini,
P.Coco,
E.Fumagalli,
P.G.Casali,
and
S.Pilotti
(2011).
Imatinib response in two GIST patients carrying two hitherto functionally uncharacterized PDGFRA mutations: An imaging, biochemical and molecular modeling study.
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Int J Cancer,
128,
983-990.
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P.M.Chan
(2011).
Differential signaling of Flt3 activating mutations in acute myeloid leukemia: a working model.
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Protein Cell,
2,
108-115.
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P.Rutkowski,
M.Dębiec-Rychter,
Z.Nowecki,
W.Michej,
M.Symonides,
K.Ptaszynski,
and
W.Ruka
(2011).
Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection.
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J Eur Acad Dermatol Venereol,
25,
264-270.
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Y.Y.Wang,
L.J.Zhao,
C.F.Wu,
P.Liu,
L.Shi,
Y.Liang,
S.M.Xiong,
J.Q.Mi,
Z.Chen,
R.Ren,
and
S.J.Chen
(2011).
C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice.
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Proc Natl Acad Sci U S A,
108,
2450-2455.
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C.Bodemer,
O.Hermine,
F.Palmérini,
Y.Yang,
C.Grandpeix-Guyodo,
P.S.Leventhal,
S.Hadj-Rabia,
L.Nasca,
S.Georgin-Lavialle,
A.Cohen-Akenine,
J.M.Launay,
S.Barete,
F.Feger,
M.Arock,
B.Catteau,
B.Sans,
J.F.Stalder,
F.Skowron,
L.Thomas,
G.Lorette,
P.Plantin,
P.Bordigoni,
O.Lortholary,
Y.de Prost,
A.Moussy,
H.Sobol,
and
P.Dubreuil
(2010).
Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.
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J Invest Dermatol,
130,
804-815.
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C.M.Wang,
K.Huang,
Y.Zhou,
C.Y.Du,
Y.W.Ye,
H.Fu,
X.Y.Zhou,
and
Y.Q.Shi
(2010).
Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors.
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J Cancer Res Clin Oncol,
136,
1065-1071.
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E.Gregory-Bryson,
E.Bartlett,
M.Kiupel,
S.Hayes,
and
V.Yuzbasiyan-Gurkan
(2010).
Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11.
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BMC Cancer,
10,
559.
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G.Tryggvason,
B.Hilmarsdottir,
G.H.Gunnarsson,
J.J.Jónsson,
J.G.Jónasson,
and
M.K.Magnússon
(2010).
Tyrosine kinase mutations in gastrointestinal stromal tumors in a nation-wide study in Iceland.
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APMIS,
118,
648-656.
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H.M.Zhang,
X.Yu,
M.J.Greig,
K.S.Gajiwala,
J.C.Wu,
W.Diehl,
E.A.Lunney,
M.R.Emmett,
and
A.G.Marshall
(2010).
Drug binding and resistance mechanism of KIT tyrosine kinase revealed by hydrogen/deuterium exchange FTICR mass spectrometry.
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Protein Sci,
19,
703-715.
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J.Call,
N.J.Scherzer,
P.D.Josephy,
and
C.Walentas
(2010).
Evaluation of self-reported progression and correlation of imatinib dose to survival in patients with metastatic gastrointestinal stromal tumors: an open cohort study.
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J Gastrointest Cancer,
41,
60-70.
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J.P.DiNitto,
G.D.Deshmukh,
Y.Zhang,
S.L.Jacques,
R.Coli,
J.W.Worrall,
W.Diehl,
J.M.English,
and
J.C.Wu
(2010).
Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance.
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J Biochem,
147,
601-609.
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K.Skobridis,
M.Kinigopoulou,
V.Theodorou,
E.Giannousi,
A.Russell,
R.Chauhan,
R.Sala,
N.Brownlow,
S.Kiriakidis,
J.Domin,
A.G.Tzakos,
and
N.J.Dibb
(2010).
Novel imatinib derivatives with altered specificity between Bcr-Abl and FMS, KIT, and PDGF receptors.
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ChemMedChem,
5,
130-139.
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L.M.Wodicka,
P.Ciceri,
M.I.Davis,
J.P.Hunt,
M.Floyd,
S.Salerno,
X.H.Hua,
J.M.Ford,
R.C.Armstrong,
P.P.Zarrinkar,
and
D.K.Treiber
(2010).
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
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Chem Biol,
17,
1241-1249.
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M.Arock,
and
P.Valent
(2010).
Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives.
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Expert Rev Hematol,
3,
497-516.
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M.Rabiller,
M.Getlik,
S.Klüter,
A.Richters,
S.Tückmantel,
J.R.Simard,
and
D.Rauh
(2010).
Proteus in the world of proteins: conformational changes in protein kinases.
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Arch Pharm (Weinheim),
343,
193-206.
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P.Ranjitkar,
A.M.Brock,
and
D.J.Maly
(2010).
Affinity reagents that target a specific inactive form of protein kinases.
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Chem Biol,
17,
195-206.
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R.Rajasekaran,
and
R.Sethumadhavan
(2010).
Exploring the cause of drug resistance by the detrimental missense mutations in KIT receptor: computational approach.
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Amino Acids,
39,
651-660.
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S.Caenepeel,
L.Renshaw-Gegg,
A.Baher,
T.L.Bush,
W.Baron,
T.Juan,
R.Manoukian,
A.S.Tasker,
A.Polverino,
and
P.E.Hughes
(2010).
Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors.
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J Exp Clin Cancer Res,
29,
96.
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S.Kalkhof,
S.Haehn,
M.Paulsson,
N.Smyth,
J.Meiler,
and
A.Sinz
(2010).
Computational modeling of laminin N-terminal domains using sparse distance constraints from disulfide bonds and chemical cross-linking.
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Proteins,
78,
3409-3427.
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S.Pati,
G.U.Gurudutta,
O.P.Kalra,
and
A.Mukhopadhyay
(2010).
The structural insights of stem cell factor receptor (c-Kit) interaction with tyrosine phosphatase-2 (Shp-2): An in silico analysis.
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BMC Res Notes,
3,
14.
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W.Pao,
and
J.Chmielecki
(2010).
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer.
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Nat Rev Cancer,
10,
760-774.
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Z.Orinska,
N.Föger,
M.Huber,
J.Marschall,
F.Mirghomizadeh,
X.Du,
M.Scheller,
P.Rosenstiel,
T.Goldmann,
A.Bollinger,
B.A.Beutler,
and
S.Bulfone-Paus
(2010).
I787 provides signals for c-Kit receptor internalization and functionality that control mast cell survival and development.
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Blood,
116,
2665-2675.
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A.Dixit,
and
G.M.Verkhivker
(2009).
Hierarchical modeling of activation mechanisms in the ABL and EGFR kinase domains: thermodynamic and mechanistic catalysts of kinase activation by cancer mutations.
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PLoS Comput Biol,
5,
e1000487.
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A.Dixit,
L.Yi,
R.Gowthaman,
A.Torkamani,
N.J.Schork,
and
G.M.Verkhivker
(2009).
Sequence and structure signatures of cancer mutation hotspots in protein kinases.
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PLoS One,
4,
e7485.
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A.Torkamani,
G.Verkhivker,
and
N.J.Schork
(2009).
Cancer driver mutations in protein kinase genes.
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Cancer Lett,
281,
117-127.
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J.A.Winger,
O.Hantschel,
G.Superti-Furga,
and
J.Kuriyan
(2009).
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).
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BMC Struct Biol,
9,
7.
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PDB code:
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J.E.Cortes,
M.J.Egorin,
F.Guilhot,
M.Molimard,
and
F.X.Mahon
(2009).
Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia.
|
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Leukemia,
23,
1537-1544.
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J.Sun,
M.Pedersen,
and
L.Rönnstrand
(2009).
The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction.
|
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J Biol Chem,
284,
11039-11047.
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K.S.Gajiwala,
J.C.Wu,
J.Christensen,
G.D.Deshmukh,
W.Diehl,
J.P.DiNitto,
J.M.English,
M.J.Greig,
Y.A.He,
S.L.Jacques,
E.A.Lunney,
M.McTigue,
D.Molina,
T.Quenzer,
P.A.Wells,
X.Yu,
Y.Zhang,
A.Zou,
M.R.Emmett,
A.G.Marshall,
H.M.Zhang,
and
G.D.Demetri
(2009).
KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.
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Proc Natl Acad Sci U S A,
106,
1542-1547.
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PDB codes:
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L.J.Yang,
J.Zou,
H.Z.Xie,
L.L.Li,
Y.Q.Wei,
and
S.Y.Yang
(2009).
Steered molecular dynamics simulations reveal the likelier dissociation pathway of imatinib from its targeting kinases c-Kit and Abl.
|
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PLoS One,
4,
e8470.
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L.N.Johnson
(2009).
Protein kinase inhibitors: contributions from structure to clinical compounds.
|
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Q Rev Biophys,
42,
1.
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M.A.Seeliger,
P.Ranjitkar,
C.Kasap,
Y.Shan,
D.E.Shaw,
N.P.Shah,
J.Kuriyan,
and
D.J.Maly
(2009).
Equally potent inhibition of c-Src and Abl by compounds that recognize inactive kinase conformations.
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Cancer Res,
69,
2384-2392.
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PDB codes:
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N.Naqvi,
M.Li,
E.Yahiro,
R.M.Graham,
and
A.Husain
(2009).
Insights into the characteristics of mammalian cardiomyocyte terminal differentiation shown through the study of mice with a dysfunctional c-kit.
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| |
Pediatr Cardiol,
30,
651-658.
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P.Dubreuil,
S.Letard,
M.Ciufolini,
L.Gros,
M.Humbert,
N.Castéran,
L.Borge,
B.Hajem,
A.Lermet,
W.Sippl,
E.Voisset,
M.Arock,
C.Auclair,
P.S.Leventhal,
C.D.Mansfield,
A.Moussy,
and
O.Hermine
(2009).
Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT.
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| |
PLoS One,
4,
e7258.
|
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R.L.van Montfort,
and
P.Workman
(2009).
Structure-based design of molecular cancer therapeutics.
|
| |
Trends Biotechnol,
27,
315-328.
|
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S.Salemi,
S.Yousefi,
D.Simon,
I.Schmid,
L.Moretti,
L.Scapozza,
and
H.U.Simon
(2009).
A novel FIP1L1-PDGFRA mutant destabilizing the inactive conformation of the kinase domain in chronic eosinophilic leukemia/hypereosinophilic syndrome.
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Allergy,
64,
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S.T.Hsu,
P.Varnai,
A.Bugaut,
A.P.Reszka,
S.Neidle,
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(2009).
A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics.
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J Am Chem Soc,
131,
13399-13409.
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PDB codes:
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T.Negri,
G.M.Pavan,
E.Virdis,
A.Greco,
M.Fermeglia,
M.Sandri,
S.Pricl,
M.A.Pierotti,
S.Pilotti,
and
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(2009).
T670X KIT mutations in gastrointestinal stromal tumors: making sense of missense.
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J Natl Cancer Inst,
101,
194-204.
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A.C.Dar,
M.S.Lopez,
and
K.M.Shokat
(2008).
Small molecule recognition of c-Src via the Imatinib-binding conformation.
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| |
Chem Biol,
15,
1015-1022.
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PDB codes:
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|
B.M.Jensen,
C.Akin,
and
A.M.Gilfillan
(2008).
Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders.
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| |
Br J Pharmacol,
154,
1572-1582.
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C.L.Corless,
and
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(2008).
Molecular pathobiology of gastrointestinal stromal sarcomas.
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Annu Rev Pathol,
3,
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D.Lietha,
and
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(2008).
Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation.
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| |
PLoS ONE,
3,
e3800.
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PDB codes:
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|
H.Chen,
C.F.Xu,
J.Ma,
A.V.Eliseenkova,
W.Li,
P.M.Pollock,
N.Pitteloud,
W.T.Miller,
T.A.Neubert,
and
M.Mohammadi
(2008).
A crystallographic snapshot of tyrosine trans-phosphorylation in action.
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| |
Proc Natl Acad Sci U S A,
105,
19660-19665.
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PDB code:
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J.Lasota,
and
M.Miettinen
(2008).
Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours.
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| |
Histopathology,
53,
245-266.
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J.Zou,
Y.D.Wang,
F.X.Ma,
M.L.Xiang,
B.Shi,
Y.Q.Wei,
and
S.Y.Yang
(2008).
Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process.
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| |
Proteins,
72,
323-332.
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L.L.Chen,
J.A.Holden,
H.Choi,
J.Zhu,
E.F.Wu,
K.A.Jones,
J.H.Ward,
R.H.Andtbacka,
R.L.Randall,
C.L.Scaife,
K.K.Hunt,
V.G.Prieto,
A.K.Raymond,
W.Zhang,
J.C.Trent,
R.S.Benjamin,
and
M.L.Frazier
(2008).
Evolution from heterozygous to homozygous KIT mutation in gastrointestinal stromal tumor correlates with the mechanism of mitotic nondisjunction and significant tumor progression.
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| |
Mod Pathol,
21,
826-836.
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M.D.Jacobs,
P.R.Caron,
and
B.J.Hare
(2008).
Classifying protein kinase structures guides use of ligand-selectivity profiles to predict inactive conformations: structure of lck/imatinib complex.
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| |
Proteins,
70,
1451-1460.
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PDB code:
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|
N.Brownlow,
A.E.Russell,
H.Saravanapavan,
M.Wiesmann,
J.M.Murray,
P.W.Manley,
and
N.J.Dibb
(2008).
Comparison of nilotinib and imatinib inhibition of FMS receptor signaling, macrophage production and osteoclastogenesis.
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Leukemia,
22,
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O.Ozer,
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K.R.Ostler,
C.Akin,
J.Anastasi,
J.W.Vardiman,
and
L.A.Godley
(2008).
The identification and characterisation of novel KIT transcripts in aggressive mast cell malignancies and normal CD34+ cells.
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Leuk Lymphoma,
49,
1567-1577.
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T.A.Binkowski,
and
A.Joachimiak
(2008).
Protein functional surfaces: global shape matching and local spatial alignments of ligand binding sites.
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BMC Struct Biol,
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Y.Mori,
T.Hirokawa,
K.Aoki,
H.Satomi,
S.Takeda,
M.Aburada,
and
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(2008).
Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling.
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Chem Pharm Bull (Tokyo),
56,
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A.Crespo,
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S.Wang,
W.Bornmann,
and
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(2007).
Rational drug redesign to overcome drug resistance in cancer therapy: imatinib moving target.
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Cancer Res,
67,
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A.Fernández,
A.Sanguino,
Z.Peng,
E.Ozturk,
J.Chen,
A.Crespo,
S.Wulf,
A.Shavrin,
C.Qin,
J.Ma,
J.Trent,
Y.Lin,
H.D.Han,
L.S.Mangala,
J.A.Bankson,
J.Gelovani,
A.Samarel,
W.Bornmann,
A.K.Sood,
and
G.Lopez-Berestein
(2007).
An anticancer C-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic.
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J Clin Invest,
117,
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A.K.Todd,
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G.N.Parkinson,
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Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter.
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Nucleic Acids Res,
35,
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A.V.Galkin,
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S.Kim,
T.L.Hood,
N.Li,
L.Li,
G.Xia,
R.Steensma,
G.Chopiuk,
J.Jiang,
Y.Wan,
P.Ding,
Y.Liu,
F.Sun,
P.G.Schultz,
N.S.Gray,
and
M.Warmuth
(2007).
Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.
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| |
Proc Natl Acad Sci U S A,
104,
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B.P.Craddock,
C.Cotter,
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Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region.
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FEBS Lett,
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B.P.Rubin,
M.C.Heinrich,
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(2007).
Gastrointestinal stromal tumour.
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Lancet,
369,
1731-1741.
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D.Mahadevan,
L.Cooke,
C.Riley,
R.Swart,
B.Simons,
K.Della Croce,
L.Wisner,
M.Iorio,
K.Shakalya,
H.Garewal,
R.Nagle,
and
D.Bearss
(2007).
A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors.
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| |
Oncogene,
26,
3909-3919.
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G.M.Verkhivker
(2007).
In silico profiling of tyrosine kinases binding specificity and drug resistance using Monte Carlo simulations with the ensembles of protein kinase crystal structures.
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| |
Biopolymers,
85,
333-348.
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G.M.Verkhivker
(2007).
Computational proteomics of biomolecular interactions in the sequence and structure space of the tyrosine kinome: deciphering the molecular basis of the kinase inhibitors selectivity.
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| |
Proteins,
66,
912-929.
|
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|
|
|
|
|
H.Chen,
J.Ma,
W.Li,
A.V.Eliseenkova,
C.Xu,
T.A.Neubert,
W.T.Miller,
and
M.Mohammadi
(2007).
A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases.
|
| |
Mol Cell,
27,
717-730.
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|
|
PDB codes:
|
|
|
|
|
|
|
|
K.W.Thiel,
and
G.Carpenter
(2007).
Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation.
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| |
Proc Natl Acad Sci U S A,
104,
19238-19243.
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L.Magnol,
M.C.Chevallier,
V.Nalesso,
S.Retif,
H.Fuchs,
M.Klempt,
P.Pereira,
M.Riottot,
S.Andrzejewski,
B.T.Doan,
J.J.Panthier,
A.Puech,
J.C.Beloeil,
M.H.de Angelis,
and
Y.Hérault
(2007).
KIT is required for hepatic function during mouse post-natal development.
|
| |
BMC Dev Biol,
7,
81.
|
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|
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|
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M.A.Seeliger,
B.Nagar,
F.Frank,
X.Cao,
M.N.Henderson,
and
J.Kuriyan
(2007).
c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty.
|
| |
Structure,
15,
299-311.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
N.C.Goddard,
A.McIntyre,
B.Summersgill,
D.Gilbert,
S.Kitazawa,
and
J.Shipley
(2007).
KIT and RAS signalling pathways in testicular germ cell tumours: new data and a review of the literature.
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| |
Int J Androl,
30,
337.
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O.Hantschel,
U.Rix,
U.Schmidt,
T.Bürckstümmer,
M.Kneidinger,
G.Schütze,
J.Colinge,
K.L.Bennett,
W.Ellmeier,
P.Valent,
and
G.Superti-Furga
(2007).
The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib.
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| |
Proc Natl Acad Sci U S A,
104,
13283-13288.
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S.R.Hubbard,
and
W.T.Miller
(2007).
Receptor tyrosine kinases: mechanisms of activation and signaling.
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Curr Opin Cell Biol,
19,
117-123.
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S.W.Cowan-Jacob,
G.Fendrich,
A.Floersheimer,
P.Furet,
J.Liebetanz,
G.Rummel,
P.Rheinberger,
M.Centeleghe,
D.Fabbro,
and
P.W.Manley
(2007).
Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia.
|
| |
Acta Crystallogr D Biol Crystallogr,
63,
80-93.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Yuzawa,
Y.Opatowsky,
Z.Zhang,
V.Mandiyan,
I.Lax,
and
J.Schlessinger
(2007).
Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
|
| |
Cell,
130,
323-334.
|
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|
PDB codes:
|
|
|
|
|
|
|
|
A.Fernández,
R.Scott,
and
R.S.Berry
(2006).
Packing defects as selectivity switches for drug-based protein inhibitors.
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| |
Proc Natl Acad Sci U S A,
103,
323-328.
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C.Akin
(2006).
Molecular diagnosis of mast cell disorders: a paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology.
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J Mol Diagn,
8,
412-419.
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J.R.Taylor,
N.Brownlow,
J.Domin,
and
N.J.Dibb
(2006).
FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance.
|
| |
Oncogene,
25,
147-151.
|
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N.M.Levinson,
O.Kuchment,
K.Shen,
M.A.Young,
M.Koldobskiy,
M.Karplus,
P.A.Cole,
and
J.Kuriyan
(2006).
A Src-like inactive conformation in the abl tyrosine kinase domain.
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| |
PLoS Biol,
4,
e144.
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PDB codes:
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|
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|
|
|
|
|
R.Jauch,
M.K.Cho,
S.Jäkel,
C.Netter,
K.Schreiter,
B.Aicher,
M.Zweckstetter,
H.Jäckle,
and
M.C.Wahl
(2006).
Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.
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| |
EMBO J,
25,
4020-4032.
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PDB codes:
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|
S.Maddipati,
and
A.Fernández
(2006).
Feature-similarity protein classifier as a ligand engineering tool.
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Biomol Eng,
23,
307-315.
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S.Sharma,
G.U.Gurudutta,
N.K.Satija,
S.Pati,
F.Afrin,
P.Gupta,
Y.K.Verma,
V.K.Singh,
and
R.P.Tripathi
(2006).
Stem cell c-KIT and HOXB4 genes: critical roles and mechanisms in self-renewal, proliferation, and differentiation.
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| |
Stem Cells Dev,
15,
755-778.
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A.Fernández
(2005).
Incomplete protein packing as a selectivity filter in drug design.
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| |
Structure,
13,
1829-1836.
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C.Tarn,
and
A.K.Godwin
(2005).
Molecular research directions in the management of gastrointestinal stromal tumors.
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| |
Curr Treat Options Oncol,
6,
473-486.
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F.P.Ross,
and
S.L.Teitelbaum
(2005).
alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology.
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Immunol Rev,
208,
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J.Lennartsson,
T.Jelacic,
D.Linnekin,
and
R.Shivakrupa
(2005).
Normal and oncogenic forms of the receptor tyrosine kinase kit.
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Stem Cells,
23,
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L.L.Chen,
M.Sabripour,
E.F.Wu,
V.G.Prieto,
G.N.Fuller,
and
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(2005).
A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors.
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Oncogene,
24,
4271-4280.
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L.L.Chen,
M.Sabripour,
R.H.Andtbacka,
S.R.Patel,
B.W.Feig,
H.A.Macapinlac,
H.Choi,
E.F.Wu,
M.L.Frazier,
and
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Imatinib resistance in gastrointestinal stromal tumors.
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Curr Oncol Rep,
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S.Neidle,
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Chemical approaches to the discovery and development of cancer therapies.
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Nat Rev Cancer,
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N.J.Dibb,
S.M.Dilworth,
and
C.D.Mol
(2004).
Switching on kinases: oncogenic activation of BRAF and the PDGFR family.
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Nat Rev Cancer,
4,
718-727.
|
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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.
|
|
Links
