in this study, the role of interaction of pi electrons on the strength of simultaneous σ-hole interactions (pnicogen, chalcogen and halogen bonds) is investigated using the quantum chemical calculations. x-ben||taz∙∙∙y1,y2,y3 complexes (x = cn, f, cl, br, ch3 , oh and nh2, taz= s-triazine and y1,y2 and y3 denotes ph2f, hsf, and clf molecules) is introduced as a model. the results show that inte...

p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells. How p53 selects target genes in the genome in a context- and tissue-specific manner remains largely obscure. There is growing evidence that the ability of p53 to bind DNA in a cooperative manner prominently influences target ge...

Negative cooperativity in enzyme reactions, in which the first event makes subsequent events less favorable, is sometimes well understood at the molecular level, but its physiological role has often been obscure. Negative cooperativity occurs in human glutathione transferase (GST) GSTP1-1 when it binds and neutralizes a toxic nitric oxide adduct, the dinitrosyl-diglutathionyl iron complex (DNDG...

Cytochrome P450 BM-3 from Bacillus megaterium catalyzed NADPH-supported indole hydroxylation under alkaline conditions with homotropic cooperativity toward indole. The activity was also found with the support of H2O2, tert-butyl hydroperoxide (tBuOOH), or cumene hydroperoxide (CuOOH). Enhanced activity and heterotropic cooperativity were observed in CuOOH-supported hydroxylation, and both the H...

Signal transduction upon binding of a ligand to a membrane protein can occur not only via allosteric conformational changes but also through fluctuations. We report a numerical study on the influence of conformational fluctuations on the cooperativity of a binding reaction in a simple model of an integral membrane receptor consisting of transmembrane helices. We find that small fluctuations lat...

A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite th...

We have investigated allosteric interactions of four closely related strychnine-like substances: Wieland-Gumlich aldehyde (WGA), propargyl Wieland-Gumlich aldehyde, strychnine, and brucine with N-methylscopolamine (NMS) on M(3) subtype of muscarinic receptor genetically modified in the second or the third extracellular loop to corresponding loops of M(2) subtype (M(3)o2 and M(3)o3 chimera). The...

Cyclic dimers and trimers of tetra-substituted benzenes, ((HOOC)2-C6H2-(NHI)2), are selected as convenient model systems for investigating NI…O=C halogen bond strength cooperativity. The four substituents in benzene chosen so that two them act acceptors (COOH) donors (NHI), shown the graphical abstract below. potential metal ion binding by each halogen-bonded aggregates is also investigated usi...

Site-directed mutagenesis of the aspartate receptor of Salmonella typhimurium (Tars) at serine 68, a residue located within the aspartate binding pocket and at the subunit interface, identified this residue as an allosteric switch in this receptor. Substitutions at this position can affect both the type and degree of binding cooperativity observed. Negative cooperativity is observed in the wild...