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PDBsum entry 6r4c
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PDB id:
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Transferase
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Title:
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Aurora-a in complex with shape-diverse fragment 57
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Structure:
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Aurora kinase a. Chain: a. Synonym: aurora 2,aurora/ipl1-related kinase 1,hark1,breast tumor- amplified kinase,serine/threonine-protein kinase 15,serine/threonine- protein kinase 6,serine/threonine-protein kinase aurora-a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: aurka, aik, airk1, ark1, aura, ayk1, btak, iak1, stk15, stk6. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.04Å
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R-factor:
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0.188
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R-free:
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0.226
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Authors:
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R.Bayliss,P.J.Mcintyre
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Key ref:
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R.Zhang
et al.
(2019).
Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase.
Chemistry,
25,
6831-6839.
PubMed id:
DOI:
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Date:
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22-Mar-19
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Release date:
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01-May-19
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PROCHECK
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Headers
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References
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O14965
(AURKA_HUMAN) -
Aurora kinase A from Homo sapiens
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Seq:
Struc:
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403 a.a.
265 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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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.2.7.11.1
- 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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Chemistry
25:6831-6839
(2019)
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PubMed id:
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Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase.
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R.Zhang,
P.J.McIntyre,
P.M.Collins,
D.J.Foley,
C.Arter,
F.von Delft,
R.Bayliss,
S.Warriner,
A.Nelson.
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ABSTRACT
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Historically, chemists have explored chemical space in a highly uneven and
unsystematic manner. As an example, the shape diversity of existing fragment
sets does not generally reflect that of all theoretically possible fragments. To
assess experimentally the added value of increased three dimensionality, a
shape-diverse fragment set was designed and collated. The set was assembled by
both using commercially available fragments and harnessing unified synthetic
approaches to sp3 -rich molecular scaffolds. The resulting set of 80
fragments was highly three-dimensional, and its shape diversity was
significantly enriched by twenty synthesised fragments. The fragment set was
screened by high-throughput protein crystallography against Aurora-A kinase,
revealing four hits that targeted the binding site of allosteric regulators. In
the longer term, it is envisaged that the fragment set could be screened against
a range of functionally diverse proteins, allowing the added value of more
shape-diverse screening collections to be more fully assessed.
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Links
