Calcium Binding Mechanism of Soybean Peptide with Histidine Alteration by Molecular Docking Analysis and Spectroscopic Methods

Abstract

Histidine (His) carries a unique heteroaromatic imidazole side chain and plays an irreplaceable role in peptides and proteins. With the current study, we aimed to determine the characteristics and functional activities of the bone density of soy peptide–calcium complexes in which a His residue was replaced by Leu (CBP-H). Soybean peptide (CBP-H) was chemically synthesized, the binding mechanism between CBP-H and calcium ions in combination was determined with bioinformatics and spectroscopy analysis, and the difference between CBP and CBP-H was investigated. Finally, we analyzed the effect of CBP and CBP-H on osteoblasts in vitro. The results showed that CBP-H could bind to calcium ions, and the calcium coordinated with the carboxyl groups of Asp and Glu in the peptide. The nitrogen atoms of the amino group and the oxygen atoms of the carboxyl group in CBP-H significantly contributed to the coordination with Ca2+. Furthermore, the binding capacity was 36.48 ± 0.09 mg/g, similar to CBP. However, both CBP and CBP-H could promote osteogenic activity, the activity of CBP-H was 127.147%, lower than CBP (121.777%). While it had the same ability to promote intracellular calcium concentration, CBP-H could upregulate 150.12% calcium ions into the intracellular, and the rate of the rise of CBP was 158.91%, further highlighting the potential of His residues for binding calcium and treating osteoporosis.

Evaluating the capability of soybean peptides as calcium ion carriers: a study through sequence analysis and molecular dynamics simulations

“…In the previous study, Gan et al found that peptide conformational changes of less than 6 Å during the reaction with calcium ions were reasonable and the peptide conformations were stable. 50 Therefore, we believe that the changes in the 10 peptides are due to the chelating effect of calcium ions and not due to problems with the simulation system and process parameter settings. Our simulation process is reliable.…”

A critical review of a typical research system for food‐derived metal‐chelating peptides: Production, characterization, identification, digestion, and absorption

“…The atoms represented by different colors are as follows: red—O, blue—N, white—H, and gray—C (Wang et al., 2021). (e) Molecular docking simulations for the DEDEQIPSHPPR–calcium complex (soybean peptide) (Gan, Kong, et al., 2022). (f) Structures of HKERVQLHIIPTAVGK (chickpea protein peptide) and its zinc complex illustrated by MOE (Mukhamedov et al., 2023).…”

Calcium-binding properties, stability, and osteogenic ability of phosphorylated soy peptide-calcium chelate

“…Among them, His mainly depends on the accumulation of cyclic side chains, and nitrogen atoms on the imidazole ring can also be used as hydrogen bond donors and acceptors with calcium ions under different conditions to improve calcium-binding ability (18). However, our study showed that the binding ability of His is obviously lower than that of Asp and Glu (19). Additionally, the primary structure of SPP contains serine residues with free hydroxyl groups, which are sites for the modification with the phosphate group, thus contributing to calcium-binding capacity (20).…”