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Xylose Isomerase (XI) is an intramolecular oxidoreductase enzyme and catalyzes the reversible conversion of ketoses and aldoses in addition to the bioconversion of ethanol from xylose in the production of bioethanol from hemicellulose. It has a broad range of industrial applications in the food and pharmaceutical sectors, particularly in the production of the sweetener high fructose corn syrup (HFCS). It is one of the most widely used industrial enzymes after protease. Taking this into consideration, four bacterial XI sources were selected based on growth temperature, i.e., psychrophile, mesophile, thermophile, and hyperthermophile, for analyzing Xylose Isomerase’s structure-function characteristics. It was found that thermophilic XI was structurally less stable than mesophilic and hyperthermophilic XI, whereas structural plasticity ran opposite towards mesophiles. The interaction of xylose isomerase (XI) with two ligands, namely Amino-2-Hydroxymethyl-Propane-1,3-Diol and (4R)-2-Methylpentane-2,4- Diol, was also studied. Mesophilic XI demonstrated better binding affinity with structurally stabilizing amino acids (Ala, Asp, Gly, Leu, and Arg). In comparison, Thermophilic XI showed nearly similar binding affinity with both Amino-2-Hydroxymethyl-Propane-1,3-Diol and (4R)-2-Methylpentane-2,4-Diol. The results of this investigation suggest that thermophilic XI, followed by mesophilic XI, would be the most appropriate for establishing process stability and sustainability in the food industry.

Human epidermal growth factor receptor 3 (HER3) is the only family member of the EGRF/HER family of receptor tyrosine kinases that lacks an active kinase domain (KD), which makes it an obligate binding partner with other receptors for its oncogenic role. When HER3 is activated in a ligand-dependent (NRG1/HRG) or independent manner, it can bind to other receptors (the most potent binding partner is HER2) to regulate many biological functions (growth, survival, nutrient sensing, metabolic regulation, etc.) through the PI3K–AKT–mTOR pathway. HER3 has been found to promote tumorigenesis, tumor growth, and drug resistance in different cancer types, especially breast and non-small cell lung cancer. Given its ubiquitous expression across different solid tumors and role in oncogenesis and drug resistance, there has been a long effort to target HER3. As HER3 cannot be targeted through its KD with small-molecule kinase inhibitors via the conventional method, pharmaceutical companies have used various other approaches, including blocking either the ligand-binding domain or extracellular domain for dimerization with other receptors. The development of treatment options with anti-HER3 monoclonal antibodies, bispecific antibodies, and different combination therapies showed limited clinical efficiency for various reasons. Recent reports showed that the extracellular domain of HER3 is not required for its binding with other receptors, which raises doubt about the efforts and applicability of the development of the HER3-antibodies for treatment. Whereas HER3-directed antibody–drug conjugates showed potentiality for treatment, these drugs are still under clinical trial. The currently understood model for dimerization-induced signaling remains incomplete due to the absence of the crystal structure of HER3 signaling complexes, and many lines of evidence suggest that HER family signaling involves more than the interaction of two members. This review article will significantly expand our knowledge of HER3 signaling and shed light on developing a new generation of drugs that have fewer side effects than the current treatment regimen for these patients.

Plastic waste is the biggest global problem in present times due to its constant bioaccumulation in the environment. During the last year, 367 Mt of plastics were produced in the world, of which 28.6 Mt correspond to polyurethane waste. Polyurethanes can be found in products such as adhesives, preservatives, and foams, and are often difficult to recycle. The fragmentation of plastic waste in the environment generates microplastics causing a long-term effect on our ecosystem. In search of its solution via bioremediation using enzymes, in our present study cutinase enzyme has been chosen, as it appears to be a novel candidate due to the wide variety of substrates it hydrolyzes and its presence in different microorganisms. According to physiochemical characteristics, it was found that microbial cutinase enzymes are majorly made up of aliphatic amino acids. A higher aliphatic index (more than 80) indicates the great thermostability of the enzyme. Moreover, the enzyme is found to be hydrophilic and structurally stable. The negative GRAVY value of the enzyme confirmed its stable interaction with water. It was also observed that all chosen protein models had an average of 91.10 % amino acids in the favorable regions of the Ramachandran plot. The studied microbial cutinase enzymes from both fungi Humicola insolens and actinobacterium Thermobifida fusca successfully coupled with the polyurethane resin monomers. The main interactions were found in the catalytic triad with bonds close to the urethane bonds of the ligand, in addition to having an average binding energy of − 6 kJ/mol. The interaction between the cutinases with the PUR resin as a ligand was found to be evident from our study with stable binding energies, which makes microbial cutinases potential enzymes for polyurethane waste bioremediation processes.

Ca2+-stimulated translocation of cytosolic phospholipase A2α (cPLA2α) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA2α preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLA2α C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and Ca2+ ions. Two Ca2+ are complexed at previously reported locations in the lipid-free C2-domain. One of these Ca2+ions, along with a third Ca2+, bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid headgroup recognition via cation–π interaction with the PC trimethylammonium group. Mutagenesis analyses confirm that Tyr96 and Asn65 function in PC binding selectivity by the C2-domain and in the regulation of cPLA2α activity. The DHPC-binding mode of the cPLA2α C2-domain, which differs from phosphatidylserine or phosphatidylinositol 4,5-bisphosphate binding by other C2-domains, expands and deepens knowledge of the lipid-binding mechanisms mediated by C2-domains.