Identification of a Novel Anti-cancer Protein, FIP-bbo, from Botryobasidium botryosum and Protein Structure Analysis using Molecular Dynamic Simulation

Abstract

Fungal immunoregulatory proteins (FIP) are effective small molecule proteins with broad-spectrum immunomodulatory and anti-cancer activities and can be potential agents for the development of clinical drugs and health food additives. In this study, a new member of FIP named FIP-bbo was obtained through Botryobasidium botryosum genome mining. FIP-bbo has the typical characteristics of FIP but is genetically distant from other FIPs. Recombinant FIP-bbo (rFIP-bbo) was produced in an optimized E. coli expression system, and the pure protein was isolated using a Ni-NTA column. Antineoplastic experiments suggested that FIP-bbo is similar to LZ-8 in inhibiting various cancer cells (Hela, Spac-1, and A549) at lower concentrations, but it is not as potent as LZ-8. The molecular mechanism by which FIP-bbo, FIP-fve, and LZ-8 are cytotoxic to cancer cells has been discussed based on molecular dynamics simulation. Point mutations that may improve the thermal stability of FIP-fve and FIP-bbo were predicted. These results not only present a new candidate protein for the development of anticancer adjuvants, but also provide an approach for designing FIPs with high anticancer activity.

Enhanced Thermostability of D-Psicose 3-Epimerase from Clostridium bolteae through Rational Design and Engineering of New Disulfide Bridges

“…To quantify the flexibility of the protein, B-factor values were introduced to describe the conformational state of sections of the protein structure. The higher the B-factor value, the more flexible the conformation of the corresponding sections [ 22 ]. Three mutation pairs (D90-A93, C175-A209 and A207-A243) with potential to form thermostability-enhancing disulfide bridges were selected because of their high B-factor values, corresponding to the most obvious degrees of thermal motion.…”

Green Technology for Fungal Protein Extraction—A Review

“…However, FIP-bbo was found to be less potent than LZ-8. Molecular dynamics simulations and predicted point mutations suggested potential improvements in the thermal stability and anticancer activity of FIP-fve and FIP-bbo, presenting new candidates for the development of anticancer adjuvants [25].…”

Delivery of Therapeutic Biopolymers Employing Silica-Based Nanosystems

“…Due to the number of physiological tasks developed by proteins and peptides [ 100 ], the following section will be structured in several epigraphs, covering the following aspects: (1) anticancer and pro-apoptotic proteins and peptides [ 101 , 102 , 103 ], (2) antibacterial proteins and peptide delivery [ 104 , 105 ], (3) immunostimulant nanoformulations, (4) nanocarriers for enzymes, and (5) delivery of growth factors as outlined in Figure 3 and detailed in Table 2 . In this review, non-therapeutic applications of peptides will be excluded.…”