1yhs: Difference between revisions

Revision as of 16:20, 3 May 2008

Crystal structure of Pim-1 bound to staurosporine

OverviewOverview

Pim-1 is an oncogene-encoded serine/threonine kinase primarily expressed in hematopoietic and germ cell lines. Pim-1 kinase was originally identified in Maloney murine leukemia virus-induced T-cell lymphomas and is associated with multiple cellular functions such as proliferation, survival, differentiation, apoptosis, and tumorigenesis (Wang, Z., Bhattacharya, N., Weaver, M., Petersen, K., Meyer, M., Gapter, L., and Magnuson, N. S. (2001) J. Vet. Sci. 2, 167-179). The crystal structures of Pim-1 complexed with staurosporine and adenosine were determined. Although a typical two-domain serine/threonine protein kinase fold is observed, the inter-domain hinge region is unusual in both sequence and conformation; a two-residue insertion causes the hinge to bulge away from the ATP-binding pocket, and a proline residue in the hinge removes a conserved main chain hydrogen bond donor. Without this hydrogen bond, van der Waals interactions with the hinge serve to position the ligand. The hinge region of Pim-1 resembles that of phosphatidylinositol 3-kinase more closely than it does other protein kinases. Although the phosphatidylinositol 3-kinase inhibitor LY294002 also inhibits Pim-1, the structure of the LY294002.Pim-1 complex reveals a new binding mode that may be general for Ser/Thr kinases.

About this StructureAbout this Structure

1YHS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002., Jacobs MD, Black J, Futer O, Swenson L, Hare B, Fleming M, Saxena K, J Biol Chem. 2005 Apr 8;280(14):13728-34. Epub 2005 Jan 17. PMID:15657054 Page seeded by OCA on Sat May 3 16:20:00 2008

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OCA

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 [[Image:1yhs.gif|left|200px]]
- {{Structure
+<!--
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+The line below this paragraph, containing "STRUCTURE_1yhs", 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=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span>
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-|GENE= PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1yhs|  PDB=1yhs  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yhs OCA], [http://www.ebi.ac.uk/pdbsum/1yhs PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yhs RCSB]</span>
-}}
 '''Crystal structure of Pim-1 bound to staurosporine'''
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 [[Category: Saxena, K.]]
 [[Category: Swenson, L.]]
-[[Category: protein kinase]]
+[[Category: Protein kinase]]
-[[Category: proto-oncogene]]
+[[Category: Proto-oncogene]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 16:20:00 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:07:46 2008''