2aqx
From Proteopedia
(New page: 200px<br /><applet load="2aqx" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aqx, resolution 2.50Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2aqx.gif|left|200px]]<br /><applet load="2aqx" size=" | + | [[Image:2aqx.gif|left|200px]]<br /><applet load="2aqx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2aqx, resolution 2.50Å" /> | caption="2aqx, resolution 2.50Å" /> | ||
'''Crystal Structure of the Catalytic and CaM-Binding domains of Inositol 1,4,5-Trisphosphate 3-Kinase B'''<br /> | '''Crystal Structure of the Catalytic and CaM-Binding domains of Inositol 1,4,5-Trisphosphate 3-Kinase B'''<br /> | ||
==Overview== | ==Overview== | ||
| - | D-Myoinositol 1,4,5-trisphophate 3-kinases (IP(3)-3Ks) play important | + | D-Myoinositol 1,4,5-trisphophate 3-kinases (IP(3)-3Ks) play important roles in metazoan cellular signaling. It has been demonstrated that mice without a functional version of IP(3)-3K isoform B are deficient in peripheral T-cells, indicating that IP(3)-3KB is essential to the developing immune system. The recent apo IP(3)-3KA structure exhibited a helix at the catalytic domain N-terminus exhibited a helix at the N-terminus of the catalytic domain, with a tryptophan indole moiety mimicking the binding mode of the substrate ATP purine ring, suggesting a mechanism of autoinhibition. Here we present the structure of the complete catalytic domain of IP(3)-3KB, including the CaM binding domain in complex with Mg(2+) and ATP. The crystal structure reveals a homodimeric arrangement of IP(3)-3KB catalytic domains, mediated via an intermolecular antiparallel beta-sheet formed from part of the CaM binding region. Residues from the putative autoinhibitory helix are rearranged into a loop configuration, with extensive interactions with the bound ATP. Mutagenesis of residues from this region reveals that substitution of the putative autoinhibitory tryptophan generates a hyperactive enzyme which retains Ca(2+)/CaM sensitivity. The IP(3)-3KB structure suggests a mechanism of enzyme activation, and raises the possibility that an interaction between IP(3)-3KB molecules may occur as part of the catalytic or regulatory cycle. |
==About this Structure== | ==About this Structure== | ||
| - | 2AQX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol-trisphosphate_3-kinase Inositol-trisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.127 2.7.1.127] Full crystallographic information is available from [http:// | + | 2AQX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol-trisphosphate_3-kinase Inositol-trisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.127 2.7.1.127] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQX OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chamberlain, P | + | [[Category: Chamberlain, P P.]] |
| - | [[Category: Cooke, M | + | [[Category: Cooke, M P.]] |
| - | [[Category: Lesley, S | + | [[Category: Lesley, S A.]] |
| - | [[Category: Sandberg, M | + | [[Category: Sandberg, M L.]] |
[[Category: Sauer, K.]] | [[Category: Sauer, K.]] | ||
[[Category: Spraggon, G.]] | [[Category: Spraggon, G.]] | ||
| Line 31: | Line 31: | ||
[[Category: kinase]] | [[Category: kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:29:58 2008'' |
Revision as of 14:30, 21 February 2008
|
Crystal Structure of the Catalytic and CaM-Binding domains of Inositol 1,4,5-Trisphosphate 3-Kinase B
Overview
D-Myoinositol 1,4,5-trisphophate 3-kinases (IP(3)-3Ks) play important roles in metazoan cellular signaling. It has been demonstrated that mice without a functional version of IP(3)-3K isoform B are deficient in peripheral T-cells, indicating that IP(3)-3KB is essential to the developing immune system. The recent apo IP(3)-3KA structure exhibited a helix at the catalytic domain N-terminus exhibited a helix at the N-terminus of the catalytic domain, with a tryptophan indole moiety mimicking the binding mode of the substrate ATP purine ring, suggesting a mechanism of autoinhibition. Here we present the structure of the complete catalytic domain of IP(3)-3KB, including the CaM binding domain in complex with Mg(2+) and ATP. The crystal structure reveals a homodimeric arrangement of IP(3)-3KB catalytic domains, mediated via an intermolecular antiparallel beta-sheet formed from part of the CaM binding region. Residues from the putative autoinhibitory helix are rearranged into a loop configuration, with extensive interactions with the bound ATP. Mutagenesis of residues from this region reveals that substitution of the putative autoinhibitory tryptophan generates a hyperactive enzyme which retains Ca(2+)/CaM sensitivity. The IP(3)-3KB structure suggests a mechanism of enzyme activation, and raises the possibility that an interaction between IP(3)-3KB molecules may occur as part of the catalytic or regulatory cycle.
About this Structure
2AQX is a Single protein structure of sequence from Mus musculus with and as ligands. Active as Inositol-trisphosphate 3-kinase, with EC number 2.7.1.127 Full crystallographic information is available from OCA.
Reference
Structural insights into enzyme regulation for inositol 1,4,5-trisphosphate 3-kinase B., Chamberlain PP, Sandberg ML, Sauer K, Cooke MP, Lesley SA, Spraggon G, Biochemistry. 2005 Nov 8;44(44):14486-93. PMID:16262249
Page seeded by OCA on Thu Feb 21 16:29:58 2008
Categories: Inositol-trisphosphate 3-kinase | Mus musculus | Single protein | Chamberlain, P P. | Cooke, M P. | Lesley, S A. | Sandberg, M L. | Sauer, K. | Spraggon, G. | ATP | MG | Calmodulin binding | Inositol | Ip3 | Ip3-3k | Ip3-3kb | Ip3k | Itpkb | Kinase
