4d0o: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 6: Line 6:
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d0o RCSB], [http://www.ebi.ac.uk/pdbsum/4d0o PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d0o RCSB], [http://www.ebi.ac.uk/pdbsum/4d0o PDBsum]</span></td></tr>
</table>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/AKP13_HUMAN AKP13_HUMAN]] Anchors cAMP-dependent protein kinase (PKA) and acts as an adapter protein to selectively couple G alpha-13 and Rho. Augments gene activation by the estrogen receptor in an element-specific and ligand-dependent manner. Activates estrogen receptor beta by a p38 MAPK-dependent pathway. Stimulates exchange activity on Rho proteins in vitro, but not on CDC42, Ras or Rac and may bind calcium ions.<ref>PMID:11546812</ref> <ref>PMID:9627117</ref> <ref>PMID:9891067</ref> <ref>PMID:11579095</ref> 
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==

Revision as of 01:15, 25 December 2014

AKAP13 (AKAP-Lbc) DH domainAKAP13 (AKAP-Lbc) DH domain

Structural highlights

4d0o is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, RCSB, PDBsum

Function

[AKP13_HUMAN] Anchors cAMP-dependent protein kinase (PKA) and acts as an adapter protein to selectively couple G alpha-13 and Rho. Augments gene activation by the estrogen receptor in an element-specific and ligand-dependent manner. Activates estrogen receptor beta by a p38 MAPK-dependent pathway. Stimulates exchange activity on Rho proteins in vitro, but not on CDC42, Ras or Rac and may bind calcium ions.[1] [2] [3] [4]

Publication Abstract from PubMed

The RhoGEF domain of AKAP-Lbc (AKAP13) catalyses nucleotide exchange on RhoA and is involved in 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-PH) domain to 2.1 A resolution. The structure reveals important differences compared to related RhoGEF proteins such as Leukemia-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 to 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 guanine nucleotide exchange factor inhibitors.

The Crystal Structure of the RhoA : AKAP-Lbc DH-PH Domain Complex.,Abdul Azeez KR, Knapp S, Fernandes JM, Klussmann E, Elkins JM Biochem J. 2014 Sep 4. PMID:25186459[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Diviani D, Soderling J, Scott JD. AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation. J Biol Chem. 2001 Nov 23;276(47):44247-57. Epub 2001 Sep 6. PMID:11546812 doi:http://dx.doi.org/10.1074/jbc.M106629200
  2. ↑ Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, Pagliai K, Gray K, Gutkind S, Segars J. Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. Oncogene. 1998 May 14;16(19):2513-26. PMID:9627117 doi:http://dx.doi.org/10.1038/sj.onc.1201783
  3. ↑ Sterpetti P, Hack AA, Bashar MP, Park B, Cheng SD, Knoll JH, Urano T, Feig LA, Toksoz D. Activation of the Lbc Rho exchange factor proto-oncogene by truncation of an extended C terminus that regulates transformation and targeting. Mol Cell Biol. 1999 Feb;19(2):1334-45. PMID:9891067
  4. ↑ Driggers PH, Segars JH, Rubino DM. The proto-oncoprotein Brx activates estrogen receptor beta by a p38 mitogen-activated protein kinase pathway. J Biol Chem. 2001 Dec 14;276(50):46792-7. Epub 2001 Sep 28. PMID:11579095 doi:http://dx.doi.org/10.1074/jbc.M106927200
  5. ↑ Abdul Azeez KR, Knapp S, Fernandes JM, Klussmann E, Elkins JM. The Crystal Structure of the RhoA : AKAP-Lbc DH-PH Domain Complex. Biochem J. 2014 Sep 4. PMID:25186459 doi:http://dx.doi.org/10.1042/BJ20140606

4d0o, resolution 2.75Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=4d0o&oldid=2233711"