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| {{STRUCTURE_2aqx| PDB=2aqx | SCENE= }} | | {{STRUCTURE_2aqx| PDB=2aqx | SCENE= }} |
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| '''Crystal Structure of the Catalytic and CaM-Binding domains of Inositol 1,4,5-Trisphosphate 3-Kinase B'''
| | ===Crystal Structure of the Catalytic and CaM-Binding domains of Inositol 1,4,5-Trisphosphate 3-Kinase B=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16262249}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16262249 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16262249}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Itpkb]] | | [[Category: Itpkb]] |
| [[Category: Kinase]] | | [[Category: Kinase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:21:50 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:55:15 2008'' |
