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Macronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Enzymes are globular proteins which are able to catalyze biochemical reactions. Enzymes accelerate the conversion of substrates into useful products in a buried pocket within the active site of the enzyme (53). In cells and organisms, most reactions are catalyzed by enzymes, which are regenerated during the course of a reaction, although not all reactions in nature require catalysis (53–55). These biological catalysts are physiologically important because they speed up the rates of reactions that would otherwise be too slow to support life (54). Enzymes accelerate the rates of such reactions by well over a million-fold, so reactions that would take years in the absence of catalysis can occur in fractions of seconds if catalyzed by the appropriate enzyme (55). Each enzyme has a specific active site where only one substrate or certain kind of substrate can bind to it for the conversion of the substrate into useful products. This phenomenon may be refered to as ‘the lock and key model’. For example, starch is the only substrate of the enzyme amylase which converts starch into soluble glucose, an essential macronutrient and energizing product. Each cell contains thousands of different enzymes that facilitate specific cellular reactions (3, 55). Like proteins, enzymes contain chains of amino acids linked together. The characteristic of each enzyme is determined by the different sequence of amino acid arrangement. When the bonds between the amino acid are weak, they may be broken by high temperatures or high levels of acids, and become inactive.
Antiviral Agents and Rational Drug Design
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Studies of the enzymes crystal structure using x-ray diffraction and molecular modelling revealed that neuraminidase is a mushroom-shaped tetrameric glycoprotein, attached to the viral membrane by a single hydrophobic sequence consisting of 29 amino acids, which can be cleaved from the surface enzymatically to enable the unadulterated polypeptide to be studied without loss of antigenic or enzymatic activity. It was found that the active site is a deep pocket located centrally on each protein subunit; composed of 18 amino acids that are highly conserved. The outer structure of the protein is much more variable.
Central Nervous System Effects of Essential Oil Compounds
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Elaine Elisabetsky, Domingos S. Nunes
Borneol 7 and isopulegol 8 (C10, monoterpenes) are α,β-saturated secondary alcohols presenting small, rigid, cyclic structures. Borneol 7 has a totally rigid structure with a small molecular volume (MV = 165.72), followed closely by myrtenol 1 (MV = 160.07) and isopulegol 8 (MV = 171.55) (Molinspiration, 2019). Molecules with higher or total rigidity are useful to reveal details of a given active site architecture, since a rigid structure does not adapt to the site by simple bonds twists. Totally rigid structures present only one conformation and are already in their minimum conformational energy, of special interest to structure-activity relationship studies because they may reveal precise information on the geometry of the active site to which they bind, with better chances of representing entirely new models for specific pharmacological activities.
Benzenesulfonamide derivatives as Vibrio cholerae carbonic anhydrases inhibitors: a computational-aided insight in the structural rigidity-activity relationships
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Marialuigia Fantacuzzi, Ilaria D’Agostino, Simone Carradori, Francesco Liguori, Fabrizio Carta, Mariangela Agamennone, Andrea Angeli, Filomena Sannio, Jean-Denis Docquier, Clemente Capasso, Claudiu T. Supuran
Although the above-mentioned trend was not completely respected and it resulted to be quite different for some substituents, we could notice that the more the linker is rigid (urea) the more the inhibition is strong. Thus, by performing these preliminary SAR considerations, we could assume that the activity profile of the derivatives library is strictly linked to the different rigidity of the compounds tail. After a preliminary calculation of the flexibility properties of representative compounds, we find out how they affect the affinity of the whole set of compounds for the different enzyme catalytic sites and, thereby, their inhibitory activities. In particular, we investigated their binding poses in both the human and bacterial enzymes through an in-depth structure-based computational study. Moreover, MD simulations of the most selective inhibitors of VchαCA revealed the high stability of the benzenesulfonamide core in the interaction with the zinc ion, assuming the usual coordination geometry. The structural determinants able to guarantee a proper interaction with the active site were found to be (i) the presence of the urea carbonyl group in the linker (9c), able to establish a water-mediated hydrogen bond with Pro191 or Thr190, and (ii) the constraint of the linker in cyclic urea, producing the highest selectivity over the hCA I and II.
Mixed and non-competitive enzyme inhibition: underlying mechanisms and mechanistic irrelevance of the formal two-site model
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
With most enzymes, it is not possible to make a clear distinction between the portion of the active site involved in the binding of the substrate and the actual catalytic site because the catalytic site also contributes to substrate stabilisation, at least to some extent. In this respect, enzymes that catalyse the covalent modification of large macromolecular substrates as endonucleases56, protein kinases/phosphatases57, proteases58 and in general, all post-translational modification enzymes, represent a notable exception. Often, this type of enzyme derives most of the affinity for their substrates from a region of the protein surface that is distinct and remote from the catalytic site. The substrate recognition site, in this case, is called an exo-site58.
Molecular docking studies, anti-Alzheimer’s disease, antidiabetic, and anti-acute myeloid leukemia potentials of narcissoside
Published in Archives of Physiology and Biochemistry, 2023
Tingting Liu, Lixia Cao, Tingting Zhang, Huan Fu
Firstly, it was used from Gaussian software program (Frisch et al.2009) to obtain optimised structures of molecules, which created files with *.sdf extension using these structures. Using these files, all calculations were made with Maestro Molecular modelling platform (version 12.2) by Schrödinger, LLC (2019a). Maestro Molecular modelling platform (version 12.2) by Schrödinger comes together from many modules. In the first module used, the protein preparation module (Friesner et al.2006, Schrödinger 2019b) was used for the preparation of proteins. There are many small proteins in the enzymes studied. The crystal structures of these proteins have been downloaded from the protein data bank site. These enzymes were initially minimised and the water molecules in the structure were removed. In the next step, the active sites of the enzymes were determined, in which the proteins in this active zone were given freedom of movement. Therefore, these proteins were enabled to interact with molecules more easily. In the next step, the molecule was prepared for calculations, the LigPrep module (Sastry et al.2013, Schrödinger 2019c) was used for this process.