Role of Pirin, an Oxidative Stress Sensor Protein, in Epithelial Carcinogenesis

Pirin is an oxidative stress (OS) sensor belonging to the functionally diverse cupin superfamily of proteins. Pirin is a suggested quercetinase and transcriptional activator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Its biological role in cancer development remains a novel area of study. This review presents accumulating evidence on the contribution of Pirin in epithelial cancers, involved signaling pathways, and as a suggested therapeutic target. Finally, we propose a model in which Pirin is upregulated by physical, chemical or biological factors involved in OS and cancer development.

Role of Pirin, an Oxidative Stress Sensor Protein, in Epithelial Carcinogenesis

Pirin is an oxidative stress (OS) sensor belonging to the functionally diverse cupin superfamily of proteins. Pirin is a suggested quercetinase and transcriptional activator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Its biological role in cancer development remains as a novel area of study. This review shows accumulating evidence on the contribution of Pirin in epithelial cancers, signaling pathways involved, and as a suggested therapeutic target. Finally, we propose a model in which Pirin is upregulated by physical, chemical or biological factors involved in OS and cancer development.

Genome-wide analysis of the cupin superfamily in cowpea (Vigna unguiculata)

Cowpea [Vigna unguiculata (L.)Walp.] is an essential food crop that is cultivated in many important arid and semi-arid regions of the world. In this study the genome-wide database of cowpea genes was accessed in search of genomic sequences coding for globulins, specifically members of the cupin superfamily, a well-documented multigenic family belonging to the globulin protein class. A total of seventy-seven genes belonging to the cupin superfamily were found and divided into six families. We classify V. unguiculata genes into two subgroups: classical cupins with one cupin domain (fifty-nine proteins) and bicupins with two cupin domains (eighteen members). In addition, a search for cupin members in other closely related species of the fabaceae family [V. angularis, V. radiatam and Phaseolus vulgaris (common bean)] was performed. Based on those data, a detailed characterization and comparison of the cupin genes on these species was performed with the aim to better understand the connection and functions of cupin proteins from different, but related, plant species. This study was the first attempt to investigate the cupin superfamily in V. unguiculata, allowing the identification of six cupins families and better understand the structural features of those proteins, such as number of domains alternative splicing.

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

Structure-guided identification of function: role of Capsicum annuum vicilin during oxidative stress

Proteins belonging to cupin superfamily are known to have critical and diverse physiological functions. However, 7S globulins family, which is also a part of cupin superfamily, were undermined as only seed storage proteins. Structure determination of native protein — Vic_CAPAN from Capsicum annuum — was carried out, and its physiological functions were explored after purifying the protein by ammonium sulfate precipitation followed by size exclusion chromatography. The crystal structure of vicilin determined at 2.16 Å resolution revealed two monomers per asymmetric unit which are juxtaposed orthogonal with each other. Vic_CAPAN consists predominately of β-sheets that folds to form a β-barrel structure commonly called cupin fold. Each monomer of Vic_CAPAN consists of two cupin fold domains, N-terminal and C-terminal, which accommodate two different ligands. A bound ligand was identified at the C-terminal cupin fold in the site presumably conserved for metabolites in the crystal structure. The ligand was confirmed to be salicylic acid through mass spectrometric analysis. A copper-binding site was further observed near the conserved ligand-binding pocket, suggesting possible superoxide dismutase activity of Vic_CAPAN which was subsequently confirmed biochemically. Vicilins from other sources did not exhibit this activity indicating functional specificity of Vic_CAPAN. Discovery of bound salicylic acid, which is a known regulator of antioxidant pathway, and revelation of superoxide dismutase activity suggest that Vic_CAPAN has an important role during oxidative stress. As salicylic acid changes the redox state of cell, it may act as a downstream signal for various pathways involved in plant biotic and abiotic stress rescue.