4D0N

AKAP13 (AKAP-Lbc) RhoGEF domain in complex with RhoA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 
    0.239 (Depositor), 0.270 (DCC) 
  • R-Value Work: 
    0.209 (Depositor), 0.250 (DCC) 
  • R-Value Observed: 
    0.211 (Depositor) 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

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This is version 1.3 of the entry. See complete history


Literature

The Crystal Structure of the Rhoa : Akap-Lbc Dh-Ph Domain Complex.

Abdul Azeez, K.R.Knapp, S.Fernandes, J.M.P.Klussmann, E.Elkins, J.M.

(2014) Biochem J 464: 231

  • DOI: https://doi.org/10.1042/BJ20140606
  • Primary Citation of Related Structures:  
    4D0N, 4D0O

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    *Structural Genomics Consortium, Oxford University, Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRANSFORMING PROTEIN RHOA185Homo sapiensMutation(s): 0 
EC: 3.6.5.2
UniProt & NIH Common Fund Data Resources
Find proteins for P61586 (Homo sapiens)
Explore P61586 
Go to UniProtKB:  P61586
PHAROS:  P61586
GTEx:  ENSG00000067560 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61586
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
A-KINASE ANCHOR PROTEIN 13373Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q12802 (Homo sapiens)
Explore Q12802 
Go to UniProtKB:  Q12802
PHAROS:  Q12802
GTEx:  ENSG00000170776 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ12802
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GDP
Query on GDP

Download Ideal Coordinates CCD File 
C [auth A]GUANOSINE-5'-DIPHOSPHATE
C10 H15 N5 O11 P2
QGWNDRXFNXRZMB-UUOKFMHZSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B],
G [auth B],
H [auth B],
I [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
EDO
Query on EDO

Download Ideal Coordinates CCD File 
E [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free:  0.239 (Depositor), 0.270 (DCC) 
  • R-Value Work:  0.209 (Depositor), 0.250 (DCC) 
  • R-Value Observed: 0.211 (Depositor) 
Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.32α = 90
b = 86.61β = 90
c = 116.82γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted GDPClick on this verticalbar to view details

Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2014-05-21
    Type: Initial release
  • Version 1.1: 2014-09-17
    Changes: Database references
  • Version 1.2: 2014-11-26
    Changes: Database references
  • Version 1.3: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other