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PDBsum entry 4d0o
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PDB id:
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Cell cycle
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Title:
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Akap13 (akap-lbc) dh domain
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Structure:
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A-kinase anchor protein 13. Chain: a, b. Fragment: rhogef domain, residues 1972-2207. Synonym: akap-13, akap-lbc, breast cancer nuclear receptor-binding auxiliary protein, guanine nucleotide exchange factor lbc, human thyroid-anchoring protein 31, lymphoid blast crisis oncogene, lbc oncogene, non-oncogenic rho gtpase-specific gtp exchange factor, protein kinase a-anchoring protein 13, prka13, p47, akap13. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.75Å
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R-factor:
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0.240
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R-free:
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0.308
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Authors:
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K.R.Abdul Azeez,L.Shrestha,T.Krojer,C.Allerston,F.Von Delft, C.Bountra,C.Arrowsmith,A.M.Edwards,S.Knapp,E.Klussmann,J.M.Elkins
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Key ref:
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K.R.Abdul Azeez
et al.
(2014).
The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.
Biochem J,
464,
231-239.
PubMed id:
DOI:
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Date:
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29-Apr-14
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Release date:
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21-May-14
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PROCHECK
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Headers
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References
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Q12802
(AKP13_HUMAN) -
A-kinase anchor protein 13 from Homo sapiens
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Seq:
Struc:
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2813 a.a.
234 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 8 residue positions (black
crosses)
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DOI no:
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Biochem J
464:231-239
(2014)
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PubMed id:
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The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.
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K.R.Abdul Azeez,
S.Knapp,
J.M.Fernandes,
E.Klussmann,
J.M.Elkins.
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ABSTRACT
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The RhoGEF (Rho GTPase guanine-nucleotide-exchange factor) domain of AKAP-Lbc
(A-kinase-anchoring protein-Lbc, also known as AKAP13) catalyses nucleotide
exchange on RhoA and is involved in the development of cardiac hypertrophy. The
RhoGEF activity of AKAP-Lbc has also been implicated in cancer. We have
determined the X-ray crystal structure of the complex between RhoA-GDP and the
AKAP-Lbc RhoGEF [DH (Dbl-homologous)-PH (pleckstrin homology)] domain to 2.1 Å
(1 Å=0.1 nm) resolution. The structure reveals important differences compared
with related RhoGEF proteins such as leukaemia-associated RhoGEF.
Nucleotide-exchange assays comparing the activity of the DH-PH domain to the DH
domain alone showed no role for the PH domain in nucleotide exchange, which is
explained by the RhoA-AKAP-Lbc structure. Comparison with a structure of the
isolated AKAP-Lbc DH domain revealed a change in conformation of the N-terminal
'GEF switch' region upon binding to RhoA. Isothermal titration calorimetry
showed that AKAP-Lbc has only micromolar affinity for RhoA, which combined with
the presence of potential binding pockets for small molecules on AKAP-Lbc,
raises the possibility of targeting AKAP-Lbc with GEF inhibitors.
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