2AQX

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

Summary for 2AQX

• Entry DOI: 10.2210/pdb2aqx/pdb
• Descriptor: PREDICTED: inositol 1,4,5-trisphosphate 3-kinase B, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: ip3k, itpkb, ip3-3k, ip3-3kb, inositol, kinase, ip3, calmodulin binding, transferase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 67974.21

Authors

Chamberlain, P.P.,Sandberg, M.L.,Sauer, K.,Cooke, M.P.,Lesley, S.A.,Spraggon, G. (deposition date: 2005-08-18, release date: 2005-12-06, Last modification date: 2024-03-13)

Primary citation

Chamberlain, P.P.,Sandberg, M.L.,Sauer, K.,Cooke, M.P.,Lesley, S.A.,Spraggon, G.
Structural insights into enzyme regulation for inositol 1,4,5-trisphosphate 3-kinase B
Biochemistry, 44:14486-14493, 2005

PubMed Abstract: 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.

PubMed: 16262249
DOI: 10.1021/bi051256q

Experimental method

X-RAY DIFFRACTION (2.5 Å)