Structural insight into the binding interactions of modeled structure of Arabidopsis thaliana urease with urea: an in silico study.

Urease (EC 3.5.1.5., urea amidohydrolase) catalyzes the hydrolysis of urea to ammonia and carbon dioxide. Urease is present to a greater abundance in plants and plays significant role related to nitrogen recycling from urea. But little is known about the structure and function of the urease derived from the Arabidopsis thaliana, the model system of choice for research in plant biology. In this study, a three-dimensional structural model of A. thaliana urease was constructed using computer-aided molecular modeling technique. The characteristic structural features of the modeled structure were then studied using atomistic molecular dynamics simulation. It was observed that the modeled structure was stable and regions between residues index (50-80, 500-700) to be significantly flexible. From the docking studies, we detected the possible binding interactions of modeled urease with urea. Ala399, Ile675, Thr398, and Thr679 residues of A. thaliana urease were observed to be significantly involved in binding with the substrate urea. We also compared the docking studies of ureases from other sources such as Canavalia ensiformis, Helicobacter pylori, and Bacillus pasteurii. In addition, we carried out mutation analysis to find the highly mutable amino acid residues of modeled A. thaliana urease. In this particular study, we observed Met485, Tyr510, Ser786, Val426, and Lys765 to be highly mutable amino acids. These results are significant for the mutagenesis analysis. As a whole, this study expounds the salient structural features as well the binding interactions of the modeled structure of A. thaliana urease.

Emerging implications of nonmammalian cytosine deaminases on cancer therapeutics.

Nonmammalian cytosine deaminases (CDs) have been investigated for last 30 years in the context of cancer therapy. The therapeutic effect of CD is based on its ability to catalyze the conversion of nontoxic prodrug 5-fluorocytosine (5FC) into the anticancer drug 5-fluorouracil (5FU) by deamination of the number 4 carbon of 5FC. This deamination property of CD has been explored to develop innovative therapeutic approach for treatment of cancer. A general overview is needed for the identification of efficient cytosine deaminases for potential use in cancer therapy. In this review, we have discussed about nonmammalian CDs for a variety of prodrug gene/enzyme therapy applications with several recent examples. Finally, we have provided a prospective on the future aspects of CDs and their applications in cancer therapy.

Synthesis and characterization of a novel chitosan based E. coli cytosine deaminase nanocomposite for potential application in prodrug enzyme therapy.

Cytosine deaminase is a non-mammalian enzyme of widespread interest for prodrug enzyme therapy due to its ability to convert prodrug 5-fluorocytosine into anticancer drug 5-fluorouracil. Cytosine deaminase enzyme has been purified to homogeneity from E. coli K-12 MTCC 1302 strain. K(m) values for cytosine and 5-fluorocytosine were found to be 0.26 mM and 1.82 mM, respectively. We developed a chitosan-entrapped cytosine deaminase nanocomposite. Atomic force microscopy and transmission electron microscopy images showed an elongated sphere shape nanocomposite with an average size of 80 nm diameter. Fourier transform infrared spectroscopy and X-ray diffraction results confirmed gel formation and entrapment of cytosine deaminase within the nanocomposite. Sustained release of cytosine deaminase from the nanocomposite up to one week depicted its potential implication in prodrug inducted enzyme therapy.