1xr1
From Proteopedia
(New page: 200px<br /> <applet load="1xr1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xr1, resolution 2.10Å" /> '''Crystal structure o...) |
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| - | [[Image:1xr1.gif|left|200px]]<br /> | + | [[Image:1xr1.gif|left|200px]]<br /><applet load="1xr1" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1xr1, resolution 2.10Å" /> | caption="1xr1, resolution 2.10Å" /> | ||
'''Crystal structure of hPim-1 kinase in complex with AMP-PNP at 2.1 A Resolution'''<br /> | '''Crystal structure of hPim-1 kinase in complex with AMP-PNP at 2.1 A Resolution'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pim-1 kinase is a member of a distinct class of serine/threonine kinases | + | Pim-1 kinase is a member of a distinct class of serine/threonine kinases consisting of Pim-1, Pim-2, and Pim-3. Pim kinases are highly homologous to one another and share a unique consensus hinge region sequence, ER-PXPX, with its two proline residues separated by a non-conserved residue, but they (Pim kinases) have <30% sequence identity with other kinases. Pim-1 has been implicated in both cytokine-induced signal transduction and the development of lymphoid malignancies. We have determined the crystal structures of apo Pim-1 kinase and its AMP-PNP (5'-adenylyl-beta,gamma-imidodiphosphate) complex to 2.1-angstroms resolutions. The structures reveal the following. 1) The kinase adopts a constitutively active conformation, and extensive hydrophobic and hydrogen bond interactions between the activation loop and the catalytic loop might be the structural basis for maintaining such a conformation. 2) The hinge region has a novel architecture and hydrogen-bonding pattern, which not only expand the ATP pocket but also serve to establish unambiguously the alignment of the Pim-1 hinge region with that of other kinases. 3) The binding mode of AMP-PNP to Pim-1 kinase is unique and does not involve a critical hinge region hydrogen bond interaction. Analysis of the reported Pim-1 kinase-domain structures leads to a hypothesis as to how Pim kinase activity might be regulated in vivo. |
==About this Structure== | ==About this Structure== | ||
| - | 1XR1 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 MG and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1XR1 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=MG:'>MG</scene> and <scene name='pdbligand=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1XR1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Barringer, K.]] | [[Category: Barringer, K.]] | ||
[[Category: Farmer, B.]] | [[Category: Farmer, B.]] | ||
| - | [[Category: Hickey, E | + | [[Category: Hickey, E R.]] |
[[Category: Kronkaitis, A.]] | [[Category: Kronkaitis, A.]] | ||
[[Category: Li, J.]] | [[Category: Li, J.]] | ||
[[Category: Mische, S.]] | [[Category: Mische, S.]] | ||
[[Category: Peng, C.]] | [[Category: Peng, C.]] | ||
| - | [[Category: Qian, K | + | [[Category: Qian, K C.]] |
[[Category: Studts, J.]] | [[Category: Studts, J.]] | ||
[[Category: Wang, L.]] | [[Category: Wang, L.]] | ||
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[[Category: protein kinase fold]] | [[Category: protein kinase fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:57:48 2008'' |
Revision as of 13:57, 21 February 2008
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Crystal structure of hPim-1 kinase in complex with AMP-PNP at 2.1 A Resolution
Overview
Pim-1 kinase is a member of a distinct class of serine/threonine kinases consisting of Pim-1, Pim-2, and Pim-3. Pim kinases are highly homologous to one another and share a unique consensus hinge region sequence, ER-PXPX, with its two proline residues separated by a non-conserved residue, but they (Pim kinases) have <30% sequence identity with other kinases. Pim-1 has been implicated in both cytokine-induced signal transduction and the development of lymphoid malignancies. We have determined the crystal structures of apo Pim-1 kinase and its AMP-PNP (5'-adenylyl-beta,gamma-imidodiphosphate) complex to 2.1-angstroms resolutions. The structures reveal the following. 1) The kinase adopts a constitutively active conformation, and extensive hydrophobic and hydrogen bond interactions between the activation loop and the catalytic loop might be the structural basis for maintaining such a conformation. 2) The hinge region has a novel architecture and hydrogen-bonding pattern, which not only expand the ATP pocket but also serve to establish unambiguously the alignment of the Pim-1 hinge region with that of other kinases. 3) The binding mode of AMP-PNP to Pim-1 kinase is unique and does not involve a critical hinge region hydrogen bond interaction. Analysis of the reported Pim-1 kinase-domain structures leads to a hypothesis as to how Pim kinase activity might be regulated in vivo.
About this Structure
1XR1 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Structural basis of constitutive activity and a unique nucleotide binding mode of human Pim-1 kinase., Qian KC, Wang L, Hickey ER, Studts J, Barringer K, Peng C, Kronkaitis A, Li J, White A, Mische S, Farmer B, J Biol Chem. 2005 Feb 18;280(7):6130-7. Epub 2004 Nov 3. PMID:15525646
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