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PDBsum entry 1dc2
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Gene regulation
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PDB id
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1dc2
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Contents |
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* Residue conservation analysis
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DOI no:
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Protein Sci
9:1120-1128
(2000)
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PubMed id:
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Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data.
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C.Yuan,
T.L.Selby,
J.Li,
I.J.Byeon,
M.D.Tsai.
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ABSTRACT
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Within the tumor suppressor protein INK4 (inhibitor of cyclin-dependent kinase
4) family, p15INK4B is the smallest and the only one whose structure has not
been determined previously, probably due to the protein's conformational
flexibility and instability. In this work, multidimensional NMR studies were
performed on this protein. The first tertiary structure was built by comparative
modeling with p16INK4A as the template, followed by restrained energy
minimization with NMR constraints (NOE and H-bonds). For this purpose, the
solution structure of pl6INK4A, whose quality was also limited by similar
problems, was refined with additional NMR experiments conducted on an 800 MHz
spectrometer and by structure-based iterative NOE assignments. The nonhelical
regions showed major improvement with root-mean-square deviation (RMSD) improved
from 1.23 to 0.68 A for backbone heavy atoms. The completion of p15INK4B coupled
with refinement of p16INK4A made it possible to compare the structures of the
four INK4 members in depth, and to compare the structures of p16INK4A in the
free form and in the p16INK4A-CDK6 complex. This is an important step toward a
comprehensive understanding of the precise functional roles of each INK4 member.
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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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B.Busby,
T.Oashi,
C.D.Willis,
M.A.Ackermann,
A.Kontrogianni-Konstantopoulos,
A.D.Mackerell,
and
R.J.Bloch
(2011).
Electrostatic interactions mediate binding of obscurin to small ankyrin 1: biochemical and molecular modeling studies.
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J Mol Biol,
408,
321-334.
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C.Kannengiesser,
S.Brookes,
A.G.del Arroyo,
D.Pham,
J.Bombled,
M.Barrois,
O.Mauffret,
M.F.Avril,
A.Chompret,
G.M.Lenoir,
A.Sarasin,
G.Peters,
B.Bressac-de Paillerets,
F.Boitier,
V.Bonadonna,
J.M.Bonnetblanc,
J.Chiesa,
I.Coupier,
S.Dalle,
F.Grange,
B.Guillot,
P.Joly,
C.Lasset,
D.Leroux,
J.M.Limacher,
M.Longy,
T.Martin-Denavit,
L.Thomas,
and
P.Vabres
(2009).
Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients.
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Hum Mutat,
30,
564-574.
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N.Fahham,
M.H.Ghahremani,
S.Sardari,
B.Vaziri,
and
S.N.Ostad
(2009).
Simulation of Different Truncated p16 Forms and In Silico Study of Interaction with Cdk4.
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Cancer Inform,
7,
1.
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G.Interlandi,
G.Settanni,
and
A.Caflisch
(2006).
Unfolding transition state and intermediates of the tumor suppressor p16INK4a investigated by molecular dynamics simulations.
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Proteins,
64,
178-192.
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J.Sridhar,
N.Akula,
and
N.Pattabiraman
(2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
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AAPS J,
8,
E204-E221.
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J.Li,
and
M.D.Tsai
(2002).
Novel insights into the INK4-CDK4/6-Rb pathway: counter action of gankyrin against INK4 proteins regulates the CDK4-mediated phosphorylation of Rb.
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Biochemistry,
41,
3977-3983.
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M.A.Blackwood,
R.Holmes,
M.Synnestvedt,
M.Young,
C.George,
H.Yang,
D.E.Elder,
L.M.Schuchter,
D.Guerry,
and
A.Ganguly
(2002).
Multiple primary melanoma revisited.
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Cancer,
94,
2248-2255.
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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.
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