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PDBsum entry 5e8t
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PDB id:
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Transferase
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Title:
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Tgf-beta receptor type 1 kinase domain (t204d)
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Structure:
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Tgf-beta receptor type-1. Chain: a. Fragment: kinase domain, unp residues 200-503. Synonym: tgfr-1,activin a receptor type ii-like protein kinase of 53kd,activin receptor-like kinase 5,alk5,serine/threonine-protein kinase receptor r4,skr4,tgf-beta type i receptor,transforming growth factor-beta receptor type i,tbetar-i. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: tgfbr1, alk5, skr4. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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1.70Å
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R-factor:
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0.170
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R-free:
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0.190
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Authors:
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S.Sheriff
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Key ref:
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A.J.Tebben
et al.
(2016).
Crystal structures of apo and inhibitor-bound TGFβR2 kinase domain: insights into TGFβR isoform selectivity.
Acta Crystallogr D Struct Biol,
72,
658-674.
PubMed id:
DOI:
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Date:
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14-Oct-15
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Release date:
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11-May-16
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PROCHECK
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Headers
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References
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P36897
(TGFR1_HUMAN) -
TGF-beta receptor type-1 from Homo sapiens
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Seq:
Struc:
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503 a.a.
302 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 3 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.11.30
- receptor protein serine/threonine kinase.
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Reaction:
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1.
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L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor- protein] + ADP + H+
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2.
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L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor- protein] + ADP + H+
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L-seryl-[receptor-protein]
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+
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ATP
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=
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O-phospho-L-seryl-[receptor- 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-[receptor-protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[receptor- 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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Acta Crystallogr D Struct Biol
72:658-674
(2016)
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PubMed id:
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Crystal structures of apo and inhibitor-bound TGFβR2 kinase domain: insights into TGFβR isoform selectivity.
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A.J.Tebben,
M.Ruzanov,
M.Gao,
D.Xie,
S.E.Kiefer,
C.Yan,
J.A.Newitt,
L.Zhang,
K.Kim,
H.Lu,
L.M.Kopcho,
S.Sheriff.
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ABSTRACT
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The cytokine TGF-β modulates a number of cellular activities and plays a
critical role in development, hemostasis and physiology, as well as in diseases
including cancer and fibrosis. TGF-β signals through two transmembrane
serine/threonine kinase receptors: TGFβR1 and TGFβR2. Multiple structures of
the TGFβR1 kinase domain are known, but the structure of TGFβR2 remains
unreported. Wild-type TGFβR2 kinase domain was refractory to crystallization,
leading to the design of two mutated constructs: firstly, a TGFβR1 chimeric
protein with seven ATP-site residues mutated to their counterparts in TGFβR2,
and secondly, a reduction of surface entropy through mutation of six charged
residues on the surface of the TGFβR2 kinase domain to alanines. These yielded
apo and inhibitor-bound crystals that diffracted to high resolution
(<2 Å). Comparison of these structures with those of TGFβR1 reveal shared
ligand contacts as well as differences in the ATP-binding sites, suggesting
strategies for the design of pan and selective TGFβR inhibitors.
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Links
