The multiple roles of histidine in protein interactions

Abstract

BackgroundAmong the 20 natural amino acids histidine is the most active and versatile member that plays the multiple roles in protein interactions, often the key residue in enzyme catalytic reactions. A theoretical and comprehensive study on the structural features and interaction properties of histidine is certainly helpful.ResultsFour interaction types of histidine are quantitatively calculated, including: (1) Cation-π interactions, in which the histidine acts as the aromatic π-motif in neutral form (His), or plays the cation role in protonated form (His+); (2) π-π stacking interactions between histidine and other aromatic amino acids; (3) Hydrogen-π interactions between histidine and other aromatic amino acids; (4) Coordinate interactions between histidine and metallic cations. The energies of π-π stacking interactions and hydrogen-π interactions are calculated using CCSD/6-31+G(d,p). The energies of cation-π interactions and coordinate interactions are calculated using B3LYP/6-31+G(d,p) method and adjusted by empirical method for dispersion energy. ConclusionsThe coordinate interactions between histidine and metallic cations are the strongest one acting in broad range, followed by the cation-π, hydrogen-π, and π-π stacking interactions. When the histidine is in neutral form, the cation-π interactions are attractive; when it is protonated (His+), the interactions turn to repulsive. The two protonation forms (and pKa values) of histidine are reversibly switched by the attractive and repulsive cation-π interactions. In proteins the π-π stacking interaction between neutral histidine and aromatic amino acids (Phe, Tyr, Trp) are in the range from -3.0 to -4.0 kcal/mol, significantly larger than the van der Waals energies.

Proteolytic activity of Crocodylus porosus transthyretin protease and role of the terminal polypeptide sequences

“…His and Tyr interact with Zn 2+ with different affinities. In solution, His mostly interacts with Zn 2+ via a coordinate interaction in which the lone electron pair of the basic N in the imidazole ring acts as a coordinate ligand for the metallic cations 33 , whereas, the Tyr and Zn 2+ complex was stabilized by a cation-π interaction, and a noncovalent binding between an aromatic π system and a metallic ion 34 . A comparative determination of the binding affinities between crocTTR and human TTR with Zn 2+ is therefore required to confirm the importance of the His residue in the HXHXE motif.…”

The sphingosine 1-phosphate breakdown product, (2E)-hexadecenal, forms protein adducts and glutathione conjugates in vitro

“…The half-life (t 1/2 ) for all amino acid adducts, except 3-His-HD, that were estimated by second-order polynomial regression using the time-courses given in Figure 4 were in the range of 11 to 19 h. Interestingly, the Michael adduct of His and 2EHD had a t 1/2 of about 45 h and therefore possessed a substantial higher stability. Due to its imidazole moiety, His plays multiple roles in molecular interactions, particularly in proteins, with hydrogen bonding interactions being an example (27). Possibly, such an intramolecular hydrogen bond between the basic imidazole nitrogen and the carbonyl function of 2EHD, present in the enol form, contributes to the stabilization of the adduct.…”

Amino Acid Composition of Ten Fish Species from Hel River, North-East India

“…Histidine is a precursor of histamine. It is required for various roles in protein interaction, growth and repair of tissue, maintenance of myelin sheaths, and is also needed in removing heavy metals from the body [2,3,12]. Glycine, one of the major components of human skin collagen together with other amino acids like alanine, proline, serine, isoleucine, and phenylalanine, form a polypeptide that promotes regrowth and tissue healing [3].…”