Biomaterial Database

The pharmacophore of debromoaplysiatoxin responsible for protein kinase C activation. 1991

F H Kong, and Y Kishi, and D Perez-Sala, and R R Rando

Department of Chemistry, Harvard University, Cambridge, MA 02138.

Protein kinase C is physiologically activated by 1,2-diacyl-sn-glycerol in the S configuration. The enzyme is also powerfully activated by structurally diverse tumor promotors. A model has been developed that demonstrates how the various tumor promotors and diacylglycerols can all be accommodated by the same binding site of the kinase. One prediction of this model concerns the structural nature of the pharmacophore in the tumor promotor debromoaplysiatoxin. This prediction is realized by synthesizing the analogs with the deduced pharmacophore and demonstrating that they are potent activators of protein kinase C. These findings provide strong experimental support for our structural model of protein kinase C activation.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008235	Lyngbya Toxins	Toxins isolated from any species of the genus LYNGBYA or similar chemicals from other sources, including mollusks and micro-organisms. These have been found to be potent tumor promoters. They are biosynthesized from TRYPTOPHAN; VALINE; and METHIONINE nonribosomally (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT).	Lyngbya Toxin,Lyngbyatoxin,Lyngbyatoxins,Toxin, Lyngbya
D009682	Magnetic Resonance Spectroscopy	Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).	In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
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
D012624	Seaweed	Multicellular marine macroalgae including some members of red (RHODOPHYTA), green (CHLOROPHYTA), and brown (PHAEOPHYCEAE) algae. They are widely distributed in the ocean, occurring from the tide level to considerable depths, free-floating (planktonic) or anchored to the substratum (benthic). They lack a specialized vascular system but take up fluids, nutrients, and gases directly from the water. They contain CHLOROPHYLL and are photosynthetic, but some also contain other light-absorbing pigments. Many are of economic importance as FOOD, fertilizer, AGAR, potash, or source of IODINE.	Macroalgae
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular