Cross-talk between amino acid residues and flavonoid derivatives: insights into their chemical recognition

Abstract

Currently, there is a general consensus that flavonoids exert their antioxidant activity through their ability to interact with a broad range of proteins, enzymes and transcription factors rather than acting as conventional hydrogen-donating antioxidants. For this, the effect of different chemical groups of the conjugated flavonoid metabolites is apparently playing a pivotal role. Yet, many questions concerning the relevant molecular mechanisms still remain open. It is therefore crucial to gain a deeper insight into the amino acid residue-flavonoid interaction. Here we show extensive theoretical thermodynamic data and structural characteristics of the interaction of chalcone, genistein, epigallocatechin gallate, and quercetin and some of its metabolites with amino acid residues. By correlating (a) the binding energies of flavonoids-amino acid residues, (b) the hydrophobicity of amino acids, and (c) the abundance of amino acid residues in the binding sites of proteins, we can conclude that flavonoids appear to be strongly bonded to only few charged hydrophilic amino acids in the protein pockets, and rather weakly bonded to the majority of amino acid residues in the binding sites. This finding strongly impacts the understanding of the chemical recognition of flavonoids and their metabolites in their interaction with proteins and would contribute to a better design of further experimental studies. Particularly, the amino acids Phe, Leu, Ile and Trp seem to play a crucial role in the dynamics of flavonoid ligands in the binding sites of proteins.

Binding of Plant Polyphenols to Serum Albumin and LDL: Healthy Implications for Heart Disease

“…There are numerous reports of PP interacting by hydrogen bonding with lipids such as cholesterol and phospholipid bilayers and cell membranes using multiple techniques. − A study in this Journal showed that tea catechins formed multiple hydrogen bonds with a phospholipid . Additional support of hydrogen bonding between PP and amino acid residues comes from molecular docking studies. − Thus, we conclude that the n value of ∼1 determined by fluorescence quenching pertains to a high-affinity site for PP binding (probably involving van der Waals and electrostatic interactions) with the Apo-B100 receptor protein of LDL. There are additional low-affinity sites (where hydrogen bonding could act as the main driving force) at the Apo-B100 surface and/or the phospholipid outer shell that also can make a contribution that can be detected by the affinity column/HPLC method.…”

Inhibition of CpLIP2 Lipase Hydrolytic Activity by Four Flavonols (Galangin, Kaempferol, Quercetin, Myricetin) Compared to Orlistat and Their Binding Mechanisms Studied by Quenching of Fluorescence

“…In addition, the binding forces between PL and QUE (among other flavonoids) presented the strongest binding combined to the highest inhibitory potency, mainly explained by its polar interactions due to its size and stringency of structure [62]. It was reported that F, L, isoleucine (I) and W residues play a major role in the dynamic of binding between proteins and flavonoid ligands according to: (i) flavonoids - amino acids (AA) binding energies, (ii) AA hydrophobicity, and (iii) the high number of AA involved in the binding sites of proteins [63].…”

Neuroprotective activities of acai berries (Euterpe sp.): A review

“…However, collective evidence demonstrates that nutritional conditions, dietary habits, bioactive compounds derived from food, and exercise prevent the age-dependent decline in memory and cognition (8)(9)(10). Many dietary foods, phytochemicals, herbal secondary metabolites, and polyphenols have pharmacological benefits for human diseases (11)(12)(13). Colourful berries, especially those rich in polyphenols, have revealed an improvement in the motor, memory, and cognitive functions that are deteriorated with aging in animals, including humans (14)(15)(16).…”