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PDBsum entry 4ifc
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PDB id:
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Transferase
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Title:
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Crystal structure of adp-bound human prpf4b kinase domain
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Structure:
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Serine/threonine-protein kinase prp4 homolog. Chain: a, b. Fragment: kinase domain. Synonym: prp4 kinase, prp4 pre-mRNA-processing factor 4 homolog. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: kiaa0536, prp4, prp4h, prp4k, prpf4b. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.13Å
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R-factor:
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0.244
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R-free:
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0.256
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Authors:
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I.Mechin,K.Haas,X.Chen,Y.Zhang,L.Mclean
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Key ref:
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Q.Gao
et al.
(2013).
Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches.
J Biol Chem,
288,
30125-30138.
PubMed id:
DOI:
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Date:
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14-Dec-12
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Release date:
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28-Aug-13
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PROCHECK
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Headers
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References
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Q13523
(PRP4B_HUMAN) -
Serine/threonine-protein kinase PRP4 homolog from Homo sapiens
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Seq:
Struc:
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1007 a.a.
328 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]
Bound ligand (Het Group name = )
corresponds exactly
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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]
Bound ligand (Het Group name = )
corresponds exactly
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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
288:30125-30138
(2013)
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PubMed id:
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Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches.
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Q.Gao,
I.Mechin,
N.Kothari,
Z.Guo,
G.Deng,
K.Haas,
J.McManus,
D.Hoffmann,
A.Wang,
D.Wiederschain,
J.Rocnik,
W.Czechtizky,
X.Chen,
L.McLean,
H.Arlt,
D.Harper,
F.Liu,
T.Majid,
V.Patel,
C.Lengauer,
C.Garcia-Echeverria,
B.Zhang,
H.Cheng,
M.Dorsch,
S.M.Huang.
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ABSTRACT
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PRP4 kinase is known for its roles in regulating pre-mRNA splicing and beyond.
Therefore, a wider spectrum of PRP4 kinase substrates could be expected. The
role of PRP4 kinase in cancer is also yet to be fully elucidated. Attaining
specific and potent PRP4 inhibitors would greatly facilitate the study of PRP4
biological function and its validation as a credible cancer target. In this
report, we verified the requirement of enzymatic activity of PRP4 in regulating
cancer cell growth and identified an array of potential novel substrates through
orthogonal proteomics approaches. The ensuing effort in structural biology
unveiled for the first time unique features of PRP4 kinase domain and its
potential mode of interaction with a low molecular weight inhibitor. These
results provide new and important information for further exploration of PRP4
kinase function in cancer.
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