4O4C: Crystal Structure Of An Inositol Hexakisphosphate Kinase Apo-ehip6ka

Citation:
Abstract
Inositol trisphosphate kinases (IP3Ks) and inositol hexakisphosphate kinases (IP6Ks) each regulate specialized signalling activities by phosphorylating either InsP3 or InsP6 respectively. The molecular basis for these different kinase activities can be illuminated by a structural description of IP6K. Here we describe the crystal structure of an Entamoeba histolytica hybrid IP6K/IP3K, an enzymatic parallel to a 'living fossil'. Through molecular modelling and mutagenesis, we extrapolated our findings to human IP6K2, which retains vestigial IP3K activity. Two structural elements, an alpha-helical pair and a rare, two-turn 310 helix, together forge a substrate-binding pocket with an open clamshell geometry. InsP6 forms substantial contacts with both structural elements. Relative to InsP6, enzyme-bound InsP3 rotates 55 degrees closer to the alpha-helices, which provide most of the protein's interactions with InsP3. These data reveal the molecular determinants of IP6K activity, and suggest an unusual evolutionary trajectory for a primordial kinase that could have favored efficient bifunctionality, before propagation of separate IP3Ks and IP6Ks.
PDB ID: 4O4CDownload
MMDB ID: 120819
PDB Deposition Date: 2013/12/18
Updated in MMDB: 2014/07
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4O4C: monomeric; determined by author and by software (PISA)
Molecular Components in 4O4C
Label Count Molecule
Protein (1 molecule)
1
Inositol Hexakisphosphate Kinase
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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