Crystal Structure of Inositol Phosphate Multikinase 2 and Implications for Substrate Specificity
Inositol polyphosphates perform essential functions as second messengers in eukaryotic cells, and their cellular levels are regulated by inositol phosphate kinases. Most of these enzymes belong to the inositol phosphate kinase superfamily, which consists of three subgroups, inositol 3-kinases, inositol phosphate multikinases, and inositol hexakisphosphate kinases. Family members share several strictly conserved signature motifs and are expected to have the same backbone fold, despite very limited overall amino acid sequence identity. Sequence differences are expected to play important roles in defining the different substrate selectivity of these enzymes. To investigate the structural basis for substrate specificity, we have determined the crystal structure of the yeast inositol phosphate multikinase Ipk2 in the apoform and in a complex with ADP and Mn{sup 2+} at up to 2.0{angstrom} resolution. The overall structure of Ipk2 is related to inositol trisphosphate 3-kinase. The ATP binding site is similar in both enzymes; however, the inositol binding domain is significantly smaller in Ipk2. Replacement of critical side chains in the inositolbinding site suggests how modification of substrate recognition motifs determines enzymatic substrate preference and catalysis.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 930219
- Report Number(s):
- BNL--80886-2008-JA
- Journal Information:
- Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 49 Vol. 281; ISSN JBCHA3; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- English
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