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PDBsum entry 4bie
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PDB id:
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Transferase
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Title:
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Crystal structures of ask1-inhibitor complexes
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Structure:
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Mitogen-activated protein kinase kinase kinase 5. Chain: a, b. Fragment: kinase domain, residues 660-977. Synonym: ask1, apoptosis signal-regulating kinase 1, ask-1, mapk/erk kinase kinase 5, mek kinase 5, mekk 5. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.36Å
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R-factor:
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0.212
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R-free:
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0.253
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Authors:
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O.Singh,A.Shillings,P.Craggs,I.Wall,P.Rowland,T.Skarzynski,C.I.Hobbs, P.Hardwick,R.Tanner,M.Blunt,D.R.Witty,K.J.Smith
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Key ref:
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O.Singh
et al.
(2013).
Crystal structures of ASK1-inhibtor complexes provide a platform for structure-based drug design.
Protein Sci,
22,
1071-1077.
PubMed id:
DOI:
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Date:
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10-Apr-13
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Release date:
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03-Jul-13
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PROCHECK
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Headers
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References
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Q99683
(M3K5_HUMAN) -
Mitogen-activated protein kinase kinase kinase 5 from Homo sapiens
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Seq:
Struc:
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1374 a.a.
257 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 1 residue position (black
cross)
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Enzyme class:
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E.C.2.7.11.25
- mitogen-activated protein kinase kinase 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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Protein Sci
22:1071-1077
(2013)
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PubMed id:
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Crystal structures of ASK1-inhibtor complexes provide a platform for structure-based drug design.
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O.Singh,
A.Shillings,
P.Craggs,
I.Wall,
P.Rowland,
T.Skarzynski,
C.I.Hobbs,
P.Hardwick,
R.Tanner,
M.Blunt,
D.R.Witty,
K.J.Smith.
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ABSTRACT
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ASK1, a member of the MAPK Kinase Kinase family of proteins has been shown to
play a key role in cancer, neurodegeneration and cardiovascular diseases and is
emerging as a possible drug target. Here we describe a 'replacement-soaking'
method that has enabled the high-throughput X-ray structure determination of
ASK1/ligand complexes. Comparison of the X-ray structures of five ASK1/ligand
complexes from 3 different chemotypes illustrates that the ASK1 ATP binding site
is able to accommodate a range of chemical diversity and different binding
modes. The replacement-soaking system is also able to tolerate some protein
flexibility. This crystal system provides a robust platform for ASK1/ligand
structure determination and future structure based drug design.
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Links
