China
Africa
Explore chapters and articles related to this topic
Peripheral Mechanisms of Mammalian Sweet Taste
Published in Robert H. Cagan, Neural Mechanisms in Taste, 2020
William Jakinovich, Dorothy Sugarman
We suggest that the mechanism is noncompetitive inhibition. An examination of the data (Figures 2 and 5 in Reference 54) indicates that the PCMB-treated sucrose response reached a new Rmax, something that would not occur in competitive inhibition. The investigators postulated that the actual mechanism of inhibition is the formation of covalent bonds with -SH groups on the receptor protein. Unfortunately, we cannot tell what occurs because of the complexity of the system. Based on the authors’ data, it would seem that all taste responses were suppressed by PCMB and NEM, with the sucrose response a bit more susceptible.
Identification Of Receptors In Vitro
Published in William C. Eckelman, Lelio G. Colombetti, Receptor-Binding Radiotracers, 2019
Just as Equation 2 is analogous to a simple situation in enzyme kinetics, Equation 13 for competitive inhibition of binding is analogous to the following situation: E + I ⇋ EI, and E + S ⇋ ES → E + P. That reaction scheme also gives an apparent change in Km, with no change in Vmax. The physical picture is that the substrate and inhibitor bind to the enzyme in a mutually exclusive manner, also analogous to the picture for competitive inhibition of binding. It is worth noting that competitive inhibition, for either enzyme or binding kinetics, does not imply that the substrate and inhibitor bind to the same physical location on the receptor or enzyme — it is enough that their bindings be mutually exclusive.
Antiepileptic Drug Interactions: An Overview
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
A number of substances inhibit phenytoin metabolism. The inhibition can be competitive or noncompetitive. With competitive inhibition, the phenytoin concentration will increase to a new steady-state value at which phenytoin has reached a new equilibrium associated with a higher phenytoin clearance. On the other hand, the introduction of a noncompetitive inhibitor will cause marked accumulation over time, with no new equilibrium being established.19
Mechanism of biotin carboxylase inhibition by ethyl 4-[[2-chloro-5-(phenylcarbamoyl)phenyl]sulphonylamino]benzoate
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Matthew K. Craft, Grover L. Waldrop
Competitive inhibition means that binding of the inhibitor and the substrate to the enzyme are mutually exclusive. This usually indicates that the inhibitor and substrate bind in the same location. The simple explanation for the competitive inhibition patterns observed for SABA1 suggest the inhibitor can bind in either the ATP or biotin binding sites, or both sites simultaneously. To determine if SABA1 can bind in the ATP binding site, biotin binding site or both, multiple inhibition analysis was performed as described by Yonetani and Theorell42. Multiple inhibition analysis is used to define the topological relationship between two different enzyme inhibitors42. Initial velocities are measured while one inhibitor is varied against fixed increasing concentrations of the second inhibitor. The substrates are held constant at subsaturating levels.
Unmasking allosteric-binding sites: novel targets for GPCR drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Verònica Casadó-Anguera, Vicent Casadó
The concept of allostery was proposed 60 years ago when the term ‘allosteric inhibition’ was used by Jacques Monod and Francois Jacob to describe a mechanism in which ‘the inhibitor is not a steric analogue of the substrate.’ Allostery consists in ‘an interaction between two topographically distinct sites on an enzyme mediated indirectly by a conformational change’ transmitted between the sites [4]. Shortly after, the mechanism underlying this conformational change was proposed to be the conformational selection. This mechanism predicts that the macromolecule exists in a thermal equilibrium between active and inactive states that can be stabilized by the binding of orthosteric or allosteric ligands to their respective (non-overlapping) binding sites [5]. This mechanism is commonly known as the concerted MWC model by Monod, Wyman, and Changeux [6]. According to this concerted model, different protomers (dimers, tetramers, …) can exist in two different states in equilibrium: a tense (T) state, which has low affinity for the ligand and is the most abundant in its absence, and a relaxed (R) state, which has high affinity for the ligand. All protomers must be in the same state at any time and ligand binding induces a concerted change of conformation of all protomers. Thus, according to this model, all protomers must be in the same conformation and symmetry has to be conserved. The oligomeric nature of the model is also able to explain the phenomenon of positive cooperativity in ligand binding, since the same ligand can bind to different protomers within the oligomer [5].
4-Arylthiosemicarbazide derivatives as a new class of tyrosinase inhibitors and anti-Toxoplasma gondii agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Adrian Bekier, Lidia Węglińska, Agata Paneth, Piotr Paneth, Katarzyna Dzitko
Two scenarios of the molecular mechanism of Tyr inhibition can be proposed from our kinetic studies. Since mixed type of inhibition has been determined quite frequently for this enzyme51, it is apparent that the inhibitor can compete with the substrate for binding space within the enzyme active site, i.e. a pocket around the iron atom, ligated by six histidines. However, two possible structural options can be considered for the other component of the inhibition, originating from the E·S·I ternary complex. The first involves the simultaneous binding of the reactant and inhibitor to the active site of the enzyme. The second consists of the inhibitor binding to an allosteric site. Detailed docking simulations excluded the first possibility on the basis of failure of binding the substrate to the enzyme-inhibitor and of biding inhibitor to enzyme-substrate complexes within the active site. This result is not surprising since the active site is quite tight and buried. Thus, only the second option remains, which is allosteric inhibition at a remote site with unknown mechanism of action or near the active site most likely with steric hindrance preventing substrate from entering/exiting while the inhibitor is bound to the protein.