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* Residue conservation analysis
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Enzyme class:
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Chain A:
E.C.2.7.11.22
- cyclin-dependent 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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DOI no:
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Cell Cycle
6:1350-1359
(2007)
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PubMed id:
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Cyclin B and cyclin A confer different substrate recognition properties on CDK2.
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N.R.Brown,
E.D.Lowe,
E.Petri,
V.Skamnaki,
R.Antrobus,
L.N.Johnson.
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ABSTRACT
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The transitions of the cell cycle are regulated by the cyclin dependent protein
kinases (CDKs). The cyclins activate their respective CDKs and confer substrate
recognition properties. We report the structure of phospho-CDK2/cyclin B and
show that cyclin B confers M phase-like properties on CDK2, the kinase that is
usually associated with S phase. Cyclin B produces an almost identical activated
conformation of CDK2 as that produced by cyclin A. There are differences between
cyclin A and cyclin B at the recruitment site, which in cyclin A is used to
recruit substrates containing an RXL motif. Because of sequence differences this
site in cyclin B binds RXL motifs more weakly than in cyclin A. Despite
similarity in kinase structures, phospho-CDK2/cyclin B phosphorylates
substrates, such as nuclear lamin and a model peptide derived from p107, at
sequences SPXX that differ from the canonical CDK2/cyclin A substrate
recognition motif, SPXK. CDK2/cyclin B phosphorylation at these non-canonical
sites is not dependent on the presence of a RXL recruitment motif. The p107
peptide contains two SP motifs each followed by a non-canonical sequence of
which only one site (Ser640) is phosphorylated by pCDK2/cyclin A while two sites
are phosphorylated by pCDK2/cyclin B. The second site is too close to the RXL
motif to allow the cyclin A recruitment site to be effective, as previous work
has shown that there must be at least 16 residues between the catalytic site
serine and the RXL motif. Thus the cyclins A and B in addition to their role in
promoting the activatory conformational switch in CDK2, also provide
differential substrate specificity.
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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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Y.Wang,
J.C.Fisher,
R.Mathew,
L.Ou,
S.Otieno,
J.Sublet,
L.Xiao,
J.Chen,
M.F.Roussel,
and
R.W.Kriwacki
(2011).
Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21.
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Nat Chem Biol,
7,
214-221.
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A.Ofir,
and
D.Kornitzer
(2010).
Candida albicans cyclin Clb4 carries S-phase cyclin activity.
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Eukaryot Cell,
9,
1311-1319.
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C.Li,
M.Andrake,
R.Dunbrack,
and
G.H.Enders
(2010).
A bifunctional regulatory element in human somatic Wee1 mediates cyclin A/Cdk2 binding and Crm1-dependent nuclear export.
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Mol Cell Biol,
30,
116-130.
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G.Kontopidis,
M.J.Andrews,
C.McInnes,
A.Plater,
L.Innes,
S.Renachowski,
A.Cowan,
and
P.M.Fischer
(2009).
Truncation and optimisation of peptide inhibitors of cyclin-dependent kinase 2-cyclin a through structure-guided design.
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ChemMedChem,
4,
1120-1128.
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PDB codes:
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T.Takaki,
A.Echalier,
N.R.Brown,
T.Hunt,
J.A.Endicott,
and
M.E.Noble
(2009).
The structure of CDK4/cyclin D3 has implications for models of CDK activation.
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Proc Natl Acad Sci U S A,
106,
4171-4176.
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PDB code:
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E.J.Ruiz,
T.Hunt,
and
A.R.Nebreda
(2008).
Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation.
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Mol Cell,
32,
210-220.
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J.Eswaran,
A.Bernad,
J.M.Ligos,
B.Guinea,
J.E.Debreczeni,
F.Sobott,
S.A.Parker,
R.Najmanovich,
B.E.Turk,
and
S.Knapp
(2008).
Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.
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Structure,
16,
115-124.
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S.Baumli,
G.Lolli,
E.D.Lowe,
S.Troiani,
L.Rusconi,
A.N.Bullock,
J.E.Debreczeni,
S.Knapp,
and
L.N.Johnson
(2008).
The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation.
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EMBO J,
27,
1907-1918.
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PDB codes:
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A.M.Bentley,
G.Normand,
J.Hoyt,
and
R.W.King
(2007).
Distinct sequence elements of cyclin B1 promote localization to chromatin, centrosomes, and kinetochores during mitosis.
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Mol Biol Cell,
18,
4847-4858.
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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
codes are
shown on the right.
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Links
