Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca(2+)- and Mg(2+)-induced association of phosphorylase kinase (PhK) from rabbit skeletal muscle has been studied at the magnitudes of the ionic strength close to the physiological values (40 mM Hepes, pH 6.8, containing 0.1 M NaCl, 0.1 mM Ca(2+), 10 mM Mg(2+); 25 degrees C) and under the molecular crowding conditions produced by high concentrations (1 M) of the natural osmolyte, trimethylamine N-oxide (TMAO). In the presence of 0.1 M NaCl two forms of PhK were registered, namely the "basic form" and "highly associated form", suggesting that PhK association may be treated as an example of cooperative association. According to the data on dynamic light scattering the average hydrodynamic radii of these forms were 16 and 144 nm. The addition of 1 M TMAO produces the time dependent increase in the light scattering intensity caused by the conversion of the basic form into the highly associated form. According to the data of the sedimentation analysis the basic form of PhK comprises a hexadecamer (M(r)=1320 kDa) and its small associates. The removal of Ca(2+) by addition of EGTA results in the reverse conversion of the highly associated form into the basic form suggesting reversibility of self-association of PhK. FAD, the ligand that is specifically bound to PhK, blocks the conversion of the basic form of PhK into the highly associated form.
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PMID:Cooperative self-association of phosphorylase kinase from rabbit skeletal muscle. 1816 37

Cell cytoplasm contains high concentrations of macromolecules occupying a significant part of the cell volume (crowding conditions). According to modern concepts, crowding has a pronounced effect on the rate and equilibrium of biochemical reactions and stimulates the formation of more compact structures. This review considers different aspects of the crowding effect in vivo and in vitro, its role in regulation of cell volume, the effect of crowding on various interactions, such as protein-ligand and protein-protein interactions, as well as on protein denaturation, conformation transitions of macromolecules, and supramolecular structure formation. The influence of crowding arising from the presence of high concentrations of osmolytes on the interactions of the enzymes of glycogenolysis has been demonstrated. It has been established that, in accordance with predictions of crowding theory, trimethylamine N-oxide (TMAO) and betaine highly stimulate the association of phosphorylase kinase (PhK) and its interaction with glycogen. However, high concentrations of proline, betaine, and TMAO completely suppress the formation of PhK complex with phosphorylase b (Phb). The protective effect of osmolyte-induced molecular crowding on Phb denaturation by guanidine hydrochloride is shown. The influence of crowding on the interaction of Phb with allosteric inhibitor FAD has been revealed. The results show that, under crowding conditions, the equilibrium of the isomerization of Phb shifts towards a more compact dimeric state with decreased affinity for FAD.
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PMID:Effect of molecular crowding on the enzymes of glycogenolysis. 1828 37