1yi3
From Proteopedia
(New page: 200px<br /> <applet load="1yi3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yi3, resolution 2.500Å" /> '''Crystal Structure ...) |
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| - | [[Image:1yi3.gif|left|200px]]<br /> | + | [[Image:1yi3.gif|left|200px]]<br /><applet load="1yi3" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yi3" size=" | + | |
caption="1yi3, resolution 2.500Å" /> | caption="1yi3, resolution 2.500Å" /> | ||
'''Crystal Structure of Pim-1 bound to LY294002'''<br /> | '''Crystal Structure of Pim-1 bound to LY294002'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pim-1 is an oncogene-encoded serine/threonine kinase primarily expressed | + | 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 Structure== | ==About this Structure== | ||
| - | 1YI3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with LY2 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1YI3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=LY2:'>LY2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YI3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Futer, O.]] | [[Category: Futer, O.]] | ||
[[Category: Hare, B.]] | [[Category: Hare, B.]] | ||
| - | [[Category: Jacobs, M | + | [[Category: Jacobs, M D.]] |
[[Category: Saxena, K.]] | [[Category: Saxena, K.]] | ||
[[Category: Swenson, L.]] | [[Category: Swenson, L.]] | ||
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[[Category: protein kinase]] | [[Category: protein kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:34 2008'' |
Revision as of 14:05, 21 February 2008
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Crystal Structure of Pim-1 bound to LY294002
Overview
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 Structure
1YI3 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
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
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