D-Histidinol

Aims: The screening of antimycobacterial benzo[d]thiazole-2-carboxamides against ATP-phosphoribosyl transferase (ATP-PRTase) was conducted. Materials & methods: The antitubercular potential of compounds 1 and 2 against ATP-PRTase was assessed through the determination of half maximal effective concentration (EC50) and binding constant (Kd), as well as competitive inhibitory studies and studies of perturbation of secondary structure, molecular modeling and L-histidine complementation assay. Results & conclusion: Compounds 1n and 2a significantly inhibited ATP-PRTase as evidenced by their EC50 and Kd values and the perturbation of the secondary structure study. Compound 1n exhibited stronger competitive inhibition toward ATP compared with 2a. The inhibition of the growth of Mycobacterium tuberculosis by targeting the L-histidine biosynthesis pathway and molecular modeling studies further supported the inhibition of ATP-PRTase.

Iron-sulfur clusters are thought to be ancient cofactors that could have played a role in early protometabolic systems. Thus far, redox active, prebiotically plausible iron-sulfur clusters have always contained cysteine ligands to the cluster. However, extant iron-sulfur proteins can be found to exploit other modes of binding, including ligation by histidine residues, as seen with [2Fe-2S] Rieske and MitoNEET proteins. Here, we investigated the ability of cysteine- and histidine-containing peptides to coordinate a mononuclear Fe2+ center and a [2Fe-2S] cluster and compare their properties with purified iron-sulfur proteins. The iron-sulfur peptides were characterized by UV-vis, circular dichroism, and paramagnetic NMR spectroscopies and cyclic voltammetry. Small (≤6 amino acids) peptides can coordinate [2Fe-2S] clusters through a combination of cysteine and histidine residues with similar reduction potentials as their corresponding proteins. Such complexes may have been important for early cell-like systems.

N-(1-Deoxy-d-fructos-1-yl)-histidine (Fru-His), one of the Amadori compounds, widely presents in processed foods, and its potential functional activities have attracted extensive attention in recent years. In this work, the angiotensin-converting enzyme (ACE) inhibitory activity and mechanism of Fru-His were investigated. The IC50 value of Fru-His was 0.150 ± 0.019 mM, and there was no obvious degradation of Fru-His after digestion simulation, showing that Fru-His has good ACE inhibition and digestive stability. Fru-His was a competitive inhibitor according to the enzyme inhibition kinetic analysis. The interaction between ACE and Fru-His occurred spontaneously mainly through hydrogen bonding, and the process was accompanied by fluorescence quenching and the alteration of the secondary structure of ACE. The molecular docking data supported the above results. Fru-His was attached to ACE's S1 active pocket through hydrogen bonds and interacted with zinc ions in active sites. The present study demonstrates that food-derived Fru-His has the potential to relieve hypertension.