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PDBsum entry 4ku7
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Signaling protein
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PDB id
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4ku7
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PDB id:
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Signaling protein
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Title:
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Structures of pkgi reveal a cgmp-selective activation mechanism
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Structure:
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Cgmp-dependent protein kinase 1. Chain: a. Fragment: carboxyl cyclic nucleotide binding domain, unp residues 204-354. Synonym: cgk 1, cgk1, cgmp-dependent protein kinase i, cgki. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: prkg1, prkg1b, prkgr1a, prkgr1b. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.65Å
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R-factor:
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0.198
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R-free:
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0.230
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Authors:
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G.Y.Huang,J.J.Kim,A.S.Reger,R.Lorenz,E.W.Moon,D.E.Casteel,B.Sankaran, F.W.Herberg,C.Kim
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Key ref:
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G.Y.Huang
et al.
(2014).
Structural basis for cyclic-nucleotide selectivity and cGMP-selective activation of PKG I.
Structure,
22,
116-124.
PubMed id:
DOI:
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Date:
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21-May-13
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Release date:
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15-Jan-14
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PROCHECK
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Headers
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References
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Q13976
(KGP1_HUMAN) -
cGMP-dependent protein kinase 1 from Homo sapiens
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Seq:
Struc:
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671 a.a.
124 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.11.12
- cGMP-dependent 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 = )
matches with 78.57% similarity
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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 = )
matches with 78.57% similarity
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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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Structure
22:116-124
(2014)
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PubMed id:
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Structural basis for cyclic-nucleotide selectivity and cGMP-selective activation of PKG I.
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G.Y.Huang,
J.J.Kim,
A.S.Reger,
R.Lorenz,
E.W.Moon,
C.Zhao,
D.E.Casteel,
D.Bertinetti,
B.Vanschouwen,
R.Selvaratnam,
J.W.Pflugrath,
B.Sankaran,
G.Melacini,
F.W.Herberg,
C.Kim.
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ABSTRACT
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Cyclic guanosine monophosphate (cGMP) and cyclic AMP (cAMP)-dependent protein
kinases (PKG and PKA) are closely related homologs, and the cyclic nucleotide
specificity of each kinase is crucial for keeping the two signaling pathways
segregated, but the molecular mechanism of cyclic nucleotide selectivity is
unknown. Here, we report that the PKG Iβ C-terminal cyclic nucleotide binding
domain (CNB-B) is highly selective for cGMP binding, and we have solved crystal
structures of CNB-B with and without bound cGMP. These structures, combined with
a comprehensive mutagenic analysis, allowed us to identify Leu296 and Arg297 as
key residues that mediate cGMP selectivity. In addition, by comparing the cGMP
bound and unbound structures, we observed large conformational changes in the
C-terminal helices in response to cGMP binding, which were stabilized by
recruitment of Tyr351 as a "capping residue" for cGMP. The observed
rearrangements of the C-terminal helices provide a mechanical insight into
release of the catalytic domain and kinase activation.
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