Quantitative Analysis and Interpretation of Allosteric Behavior

A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods

“…Although cooperativity can occur in monomeric enzymes 27 , allosteric interactions in cathepsin K ensue in the absence of cooperativity as in many other systems 28 . Hyperbolic mixed modification is the fundamental mechanism of allosteric interactions, which occurs in different variants of the general modifier mechanism 29 . To determine the kinetic parameters, additional kinetic experiments were performed and are presented in Fig.…”

Stimulation of Histone Deacetylase Activity by Metabolites of Intermediary Metabolism

“…Q is the opposite ratio of the corresponding K m values (K m(0) /K m(inf) ) ( Table 1) (24). The product WQ is Ͼ1 for enzyme activation, which is the case for both NADPH and acetyl-CoA (Table 1).…”

“…Detailed kinetic analysis (24) showed that CoA derivatives and NADPH cause mixed activation of recombinant HDAC2, affecting both the affinity of the enzyme for the substrate as well as its catalytic activity. Inhibition by free CoA is substrate-independent and is characterized by decreased reaction velocity while at the same time increasing the affinity of the enzyme for histones.…”

Allostery

“…A second driving force for the recent interest is a growing appreciation that allosteric drugs offer safety advantages over conventional drugs (7)(8)(9). This renewed interest has resulted in several reviews on allostery (10)(11)(12)(13).…”

“…The 1965 reference has been used to suggest that the recent introduction of dynamics into the discussion of allostery offers a "new view" of allostery (3,18,19). Others have relied on the 1963 definition to emphasize that the original definition of allostery placed no constraints on the molecular source of allosteric regulation and that dynamics were always accounted for in the description of this phenomena (11,12,20,21).…”