Biomaterial Database

Molecular interactions of endogenous D-myo-inositol phosphates with the intracellular D-myo-inositol 1,4,5-trisphosphate recognition site. 1994

P J Lu, and D M Gou, and W R Shieh, and C S Chen

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Rhode Island, Kingston 02881.

A systematic effort was made to elucidate the mode of recognition at the inositol 1,4,5-trisphosphate-specific receptor. Eleven D-myo-inositol phosphates were synthesized and tested for Ca(2+)-mobilizing and receptor-binding activities, which included Ins(1,3,4,5,6)P5, Ins(1,2,5,6)P4, Ins(1,3,4,5)P4, Ins(1,3,4,6)P4, Ins(1,4,5,6)P4, Ins(3,4,5,6)P4, Ins(1,3,4)P4, Ins(1,4,5)P3, Ins(1,5,6)P3, Ins(1,4)P2, and Ins(4,5)P2. Of these, Ins(1,4,5)P3, Ins(1,3,4,6)P4, Ins(1,3,4,5)P4, Ins(1,4,5,6)P4, and Ins(4,5)P2 were able to elicit Ca2+ release from rat brain microsomes. Binding experiments suggest that the ability of these polyphosphates to effect Ca2+ mobilization arises from interactions with the Ins(1,4,5)P3-specific receptor. Accordingly, a model accounting for the ligand recognition is proposed. The Ins(1,4,5)P3-binding site is presumably composed of two domains. The anchoring domain binds the 4,5-bisphosphate 6-hydroxy motif. Disruption of this structural feature abolishes the agonist activity. The auxiliary domain exerts long-range interactions with the 1-phosphate, thus enhancing the binding affinity. The stereochemical requirement for this electrostatic interaction is, however, less stringent. Evidence suggests that Ca(2+)-mobilizing inositol phosphates are able to effect productive binding by assuming conformations displaying or mimicking these essential structural features.

UI	MeSH Term	Description	Entries
D007295	Inositol Phosphates	Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.	Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002531	Cerebellum	The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.	Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000241	Adenosine	A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.	Adenocard,Adenoscan
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer