Format

Send to

Choose Destination
Adv Biol Regul. 2013 Jan;53(1):19-27. doi: 10.1016/j.jbior.2012.10.002. Epub 2012 Oct 11.

Structural insight into inositol pyrophosphate turnover.

Author information

1
Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, PO Box 12233, NC 27709, USA. Shears@niehs.nih.gov

Abstract

The diphosphoinositol polyphosphates ("inositol pyrophosphates"; PP-InsPs) regulate many cellular processes in eukaryotes, including stress responses, apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, telomere maintenance, insulin signaling and neutrophil activation. Thus, the enzymes that control the metabolism of the PP-InsPs serve important cell signaling roles. In order to fully characterize how these enzymes are regulated, we need to determine the atomic-level architecture of their active sites. Only then can we fully appreciate reaction mechanisms and their modes of regulation. In this review, we summarize published information obtained from the structural analysis of a human diphosphoinositol polyphosphate phosphohydrolase (DIPP), and a human diphosphoinositol polyphosphate kinase (PPIP5K). This work includes the analysis of crystal complexes with substrates, products, transition state analogs, and a novel phosphonoacetate substrate analog.

PMID:
23107997
PMCID:
PMC3570603
DOI:
10.1016/j.jbior.2012.10.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center