2qlu: Difference between revisions

Revision as of 15:10, 4 May 2008

Crystal structure of Activin receptor type II kinase domain from human

OverviewOverview

Activin receptor type IIB (ActRIIB), a type II TGF-beta serine/threonine kinase receptor, is integral to the activin and myostatin signaling pathway. Ligands such as activin and myostatin bind to activin type II receptors (ActRIIA, ActRIIB), and the GS domains of type I receptors are phosphorylated by type II receptors. Myostatin, a negative regulator of skeletal muscle growth, is regarded as a potential therapeutic target and binds to ActRIIB effectively, and to a lesser extent, to ActRIIA. The high-resolution structure of human ActRIIB kinase domain in complex with adenine establishes the conserved bilobal architecture consistent with all other catalytic kinase domains. The crystal structure reveals that the adenine has a considerably different orientation from that of the adenine moiety of ATP observed in other kinase structures due to the lack of an interaction by ribose-phosphate moiety and the presence of tautomers with two different protonation states at the N9 nitrogen. Although the Lys217-Glu230 salt bridge is absent, the unphosphorylated activation loop of ActRIIB adopts a conformation similar to that of the fully active form. Unlike the type I TGF-beta receptor, where a partially conserved Ser280 is a gatekeeper residue, the AcRIIB structure possesses Thr265 with a back pocket supported by Phe247. Taken together, these structural features provide a molecular basis for understanding the coupled activity and recognition specificity for human ActRIIB kinase domain and for the rational design of selective inhibitors.

About this StructureAbout this Structure

2QLU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution., Han S, Loulakis P, Griffor M, Xie Z, Protein Sci. 2007 Oct;16(10):2272-7. PMID:17893364 Page seeded by OCA on Sun May 4 15:10:21 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2qlu.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2qlu |SIZE=350|CAPTION= <scene name='initialview01'>2qlu</scene>, resolution 2.&Aring;
+The line below this paragraph, containing "STRUCTURE_2qlu", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2qlu|  PDB=2qlu  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qlu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qlu OCA], [http://www.ebi.ac.uk/pdbsum/2qlu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qlu RCSB]</span>
-}}
 '''Crystal structure of Activin receptor type II kinase domain from human'''
@@ Line 27: / Line 24: @@
 [[Category: Single protein]]
 [[Category: Han, S.]]
-[[Category: actriib]]
+[[Category: Actriib]]
-[[Category: alternative splicing]]
+[[Category: Alternative splicing]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: disease mutation]]
+[[Category: Disease mutation]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: magnesium]]
+[[Category: Magnesium]]
-[[Category: manganese]]
+[[Category: Manganese]]
-[[Category: membrane]]
+[[Category: Membrane]]
-[[Category: metal-binding]]
+[[Category: Metal-binding]]
-[[Category: nucleotide-binding]]
+[[Category: Nucleotide-binding]]
-[[Category: serine/threonine kinase receptor]]
+[[Category: Serine/threonine kinase receptor]]
-[[Category: serine/threonine-protein kinase]]
+[[Category: Serine/threonine-protein kinase]]
-[[Category: tgf-beta]]
+[[Category: Tgf-beta]]
-[[Category: transferase]]
+[[Category: Transferase]]
-[[Category: transmembrane]]
+[[Category: Transmembrane]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 15:10:21 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:50:39 2008''