2aqx

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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'''
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===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.
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{{ABSTRACT_PUBMED_16262249}}
==About this Structure==
==About this Structure==
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[[Category: Itpkb]]
[[Category: Itpkb]]
[[Category: Kinase]]
[[Category: Kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:21:50 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:55:15 2008''

Revision as of 03:55, 29 July 2008

Image:2aqx.png

Template:STRUCTURE 2aqx

Crystal Structure of the Catalytic and CaM-Binding domains of Inositol 1,4,5-Trisphosphate 3-Kinase B

Template:ABSTRACT PUBMED 16262249

About this Structure

2AQX is a Single protein structure of sequence from Mus musculus. 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 Tue Jul 29 06:55:15 2008

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