English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Inositol 1,4,5-trisphosphate receptors (IP 3 R) are intracellular Ca 2+  channels. Most animal cells express mixtures of the three IP 3 R subtypes encoded by vertebrate genomes. Adenophostin A (AdA) is the most potent naturally occurring agonist of IP 3 R and it shares with IP 3  the essential features of all IP 3 R agonists, namely structures equivalent to the 4,5-bisphosphate and 6-hydroxyl of IP 3 . The two essential phosphate groups contribute to closure of the clam-like IP 3 -binding core (IBC), and thereby IP 3 R activation, by binding to each of its sides (the α- and β-domains). Regulation of the three subtypes of IP 3 R by AdA and its analogues has not been examined in cells expressing defined homogenous populations of IP 3 R. We measured Ca 2+  release evoked by synthetic adenophostin A (AdA) and its analogues in permeabilized DT40 cells devoid of native IP 3 R and stably expressing single subtypes of mammalian IP 3 R. The determinants of high-affinity binding of AdA and its analogues were indistinguishable for each IP 3 R subtype. The results are consistent with a cation-π interaction between the adenine of AdA and a conserved arginine within the IBC α-domain contributing to closure of the IBC. The two complementary contacts between AdA and the α-domain (cation-π interaction and 3″-phosphate) allow activation of IP 3 R by an analogue of AdA (3″-dephospho-AdA) that lacks a phosphate group equivalent to the essential 5-phosphate of IP 3 . These data provide the first structure-activity analyses of key AdA analogues using homogenous populations of all mammalian IP 3 R subtypes. They demonstrate that differences in the Ca 2+  signals evoked by AdA analogues are unlikely to be due to selective regulation of IP 3 R subtypes.

Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Adenophostin A and Its Analogues