Projects / Programmes
Structural studies of inositol polyphosphate kinases
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
| P310 |
Natural sciences and mathematics |
Proteins, enzymology |
| P250 |
Natural sciences and mathematics |
Condensed matter: structure, thermal and mechanical properties, crystallography, phase equilibria |
| T490 |
Technological sciences |
Biotechnology |
inositol-phosphate, kinase, crystal structure, X-ray crystallography, phosphorilation, enzymatic versatility, enzymatic specificity
Researchers (5)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0104 |
National Institute of Chemistry |
Ljubljana |
5051592000 |
10 |
Abstract
A multiplicity of inositol phosphates exists in biology, with functions in many diverse aspects of cell biology, such as ion channel physiology, membrane dynamics and nuclear signaling. This diversity involves a whole array of proteins that either metabolize inositol phosphates or mediate their intracellular functions. Recently, a family of inositol phosphate kinases was identified whose members are conserved from yeast to humans. Some of these kinases are highly specific for their substrates, and on the other hand there are inositol phosphate kinases that phosphorylate a wide array of substrates. What is the structural basis for this contrasting situation. Three-dimensional structures of the inositol phosphate kinases are not known yet and their primary structures show no significant similarity to the well studied protein kinases or phosphoinositide kinases. It is believed that different substrates can bind to the same protein in a limited number of the binding modes. These binding modes must have recognition elements which are common both in nature (phosphate and hydroxyl groups) and orientation around the inositol ring in each of these modes. This mandatory substrate recognition features are proposed to act in concert with certain other groups that define substrate recognition in a mode-specific manner. The aim of the presented proposal is to study the versatility of the inositol phosphate kinases and their substrates using X-ray crystallography as the main technique. As a model system, we will study the structures of inositol hexakisphosphate kinase (InsP6K) and inositol phosphate multikinase (IPMK) alone and with their substrates. It is expected that these structures will help us understand and explain the complexity of the inositol phosphate metabolism. Additionally, we hope that the insight into the structural basis of the inositol phosphate turn-over will contribute to development of the knowledge about the biological functions of the inositol phosphates, especially inositol pyrophosphates.
