NOPR Collection:

Contrasting effects of mutating active site residues, Aspartic acid 64 and Histidine 187 of Escherichia coli uracil-DNA glycosylase on uracil excision and interaction with an inhibitor protein

2012-12-08T16:31:25Z

Title: Contrasting effects of mutating active site residues, Aspartic acid 64 and Histidine 187 of Escherichia coli uracil-DNA glycosylase on uracil excision and interaction with an inhibitor protein Authors: Handa, Priya; Acharya, Narottam; Talawar, Ramappa K; Roy, Sudipta; Varshney, Umesh Abstract: Uracil, a promutagenic base, arises in DNA by spontaneous deamination of cytosine or by the malfunctioning of DNA polymerases. To maintain the genomic integrity, cells possess a highly conserved base excision repair enzyme. uracil –DNA glycosylase (UDG). UDGs have a notably high turnover number and strict specificity for uracil in DNA. UDGs are inhibited by a small proteinaceous inhibitor. Ugi, which acts as a transition state substrate mimic. Crystal structure studies have identified the residues crucial in catalysis, and in their interaction with Ugi. Here, we report on the mutational analyses of D64(D64H and D64N) and H187 (H187C, H187L and H187R) in the active site pocket of Escherichia coli UDG. The mutants were compromised in uracil excision by ~ 200-25,000 fold when compared to the native protein. In contrast. our analysis of the in vivo formed UDG-Ugi complexes on urea gels shows that D64 and H187 contribute minimally to the interaction of the two proteins. Thus, our findings prov de further evidence to the primary functi on of D64 and H187 in catalysis. Page(s): 312-317

Essential fatty acids in maternal and infant nutrition

2012-12-11T16:31:25Z

Title: Essential fatty acids in maternal and infant nutrition Authors: Gopalan, C; Patnaik, Rita Page(s): 303-311

Proteomics-A new player in the post-genomic era

2012-12-08T16:31:19Z

Title: Proteomics-A new player in the post-genomic era Authors: Maithal, Kapil Abstract: In the post-genomic era the concept of personalized medicine and molecular medicine emphasizes the utility of the proteomics approach. Proteomics is the global analysis of cellular proteins and complements the genomics approach. Proteins, in principle do all the work of the cell and ultimately dictate all biological processes and the cellular fate. Proteomics uses a combination of sophisticated techniques including two-dimensional (2D) gel electrophoresis, image analysis, mass spectrometry, amino acid sequencing and bioinformatics to identify and characterize proteins. This review aims at providing the various approaches and pitfalls associated with this technique and gives a brief overview of the utility of this approach in the area of biomedical research. Page(s): 291-302

Quantitative structure-activity relationship study on N-(pyridin-4-yl)-(indol-3-yl) alkylamides as antiallergic agents

2012-12-09T16:31:30Z

Title: Quantitative structure-activity relationship study on N-(pyridin-4-yl)-(indol-3-yl) alkylamides as antiallergic agents Authors: Singh, P; Sharma, B K; Kumar, R Abstract: The antihistamine activit y of N-(pyridin -4-yl)-(indol-3 -y l) alkylamides has been analyzed using Fujita-Ban and Hansch approaches. The analyses have helped to ascertain the role of different substituents in explaining the antiallergic actions of these analogues. From both approaches it is revealed that the small size substituents at R and R₂ and non-hydrogen bond acceptor substituent at R improve histamine antagonist activity of a compound. Likewise, a small incision such as - CH₂CONH-serving as the spacer between pyridinyl and indolyl rings and a bigger substituent like 4-FBn at R₁ are also desirable for inhibitory activity. Page(s): 351-355