Molecular Recognition of Adenophostin, a Very Potent Ca2+ Inducer, at the d-myo-Inositol 1,4,5-Trisphosphate Receptor
- 29 June 1999
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 38 (29) , 9234-9241
- https://doi.org/10.1021/bi990114r
Abstract
The recognition mode of adenophostin A at the d-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor was investigated. Comparison of conformations of Ins(1,4,5)P3 and adenophostin A by using the combination of NMR and molecular mechanics (MM) calculations demonstrated that adenophostin A adopted a moderately extended conformation regarding the distance between the 2‘-phosphoryl group and the 3‘ ‘,4‘ ‘-bisphosphate motif, as suggested previously [Wilcox, R. A. et al. (1995) Mol. Pharmacol. 47, 1204−1211]. Based on the nuclear Overhauser effect (NOE) observed between 3‘-H and 1‘ ‘-H and on MM calculations, the molecular shape of adenophostin A proved to be an extended form at least in solution, in contrast to Wilcox's compactly folded, preliminary hairpin model. GlcdR(2,3‘,4‘)P3, an adenophostin analogue without adenine moiety, was found to be less potent than adenophostin A and almost equipotent to Ins(1,4,5)P3. We propose the possibility that (i) the optimal spatial arrangement of the three phosphoryl groups and/or (ii) the interaction of the adenine moiety of adenophostin A with the putative binding site, if it exists in the vicinity of the Ins(1,4,5)P3-binding site, might account for the exceptional potency of adenophostin A.Keywords
This publication has 13 references indexed in Scilit:
- Simplification of adenophostin A defines a minimal structure for potent glucopyranoside-based mimics of 1,4,5-trisphosphateBioorganic & Medicinal Chemistry Letters, 1999
- Synthesis of 1-0-[(3S,4R)-3-hydroxytetrahydrofuran-4-yl]-α-D-glucopyranoside 3,4,3′-trisphosphate as a novel potent IP3 receptor ligandTetrahedron Letters, 1998
- Synthesis of Clustered Disaccharide Polyphosphate Analogues of Adenophostin ATetrahedron Letters, 1997
- Adenophostin A Can Stimulate Ca2+ Influx without Depleting the Inositol 1,4,5-Trisphosphate-sensitive Ca2+ Stores in the Xenopus OocytePublished by Elsevier ,1997
- 6-Deoxy-6-hydroxymethyl scyllo-inositol 1,2,4-trisphosphate: A potent agonist at the inositol 1,4,5-trisphosphate receptorBioorganic & Medicinal Chemistry Letters, 1996
- IP3 Receptor-Ligand. 1: Synthesis of Adenophostin ATetrahedron Letters, 1995
- Molecular interactions of endogenous D-myo-inositol phosphates with the intracellular D-myo-inositol 1,4,5-trisphosphate recognition siteBiochemistry, 1994
- How do the gauche and anomeric effects drive the pseudorotational equilibrium of the pentofuranose moiety of nucleosides?Journal of the American Chemical Society, 1993
- Synthesis of racemic 5-phosphonate analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphateCarbohydrate Research, 1992
- Conformational analysis of the sugar ring in nucleosides and nucleotides. Improved method for the interpretation of proton magnetic resonance coupling constantsJournal of the American Chemical Society, 1973