1z2p

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1z2p, resolution 1.22Å

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Inositol 1,3,4-trisphosphate 5/6-Kinase in complex with Mg2+/AMP-PCP/Ins(1,3,4)P3

Overview

Inositol hexakisphosphate and other inositol high polyphosphates have diverse and critical roles in eukaryotic regulatory pathways. Inositol 1,3,4-trisphosphate 5/6-kinase catalyzes the rate-limiting step in inositol high polyphosphate synthesis in animals. This multifunctional enzyme also has inositol 3,4,5,6-tetrakisphosphate 1-kinase and other activities. The structure of an archetypal family member, from Entamoeba histolytica, has been determined to 1.2 A resolution in binary and ternary complexes with nucleotide, substrate, and product. The structure reveals an ATP-grasp fold. The inositol ring faces ATP edge-on such that the 5- and 6-hydroxyl groups are nearly equidistant from the ATP gamma-phosphate in catalytically productive phosphoacceptor positions and explains the unusual dual site specificity of this kinase. Inositol tris- and tetrakisphosphates interact via three phosphate binding subsites and one solvent-exposed site that could in principle be occupied by 18 different substrates, explaining the mechanisms for the multiple specificities and catalytic activities of this enzyme.

About this Structure

1Z2P is a Single protein structure of sequence from Eukaryota with , and as ligands. Full crystallographic information is available from OCA.

Reference

Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase., Miller GJ, Wilson MP, Majerus PW, Hurley JH, Mol Cell. 2005 Apr 15;18(2):201-12. PMID:15837423

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