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spinqualitylabelsall models 2aqx, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 MG and ATP 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

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