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    Structural characterization of recombinant bovine Go alpha by spectroscopy and homology modeling
    (IOS PRESS, 2011-01-01) Tiber, Pinar Mega; Orun, Oya; Nacar, Cevdet; Sezerman, Ugur Osman; Severcan, Feride; Severcan, Mete; Matagne, Andre; Kan, Beki
    Go, a member of heterotrimeric guanine nucleotide-binding proteins, is the most abundant form of G protein in the central and peripheral nervous systems. Go alpha has a significant role in neuronal development and function but its signal transduction mechanism remains to be clarified. In this study, the bovine Go alpha subunit was overexpressed and purified into homogeneity. Its activity was studied using {[}S-35] GTP gamma S binding, intrinsic fluorescence and BODIPY assays. The secondary structure was determined by both FTIR and CD spectroscopy as 42.3\% alpha-helix, 13.4\% beta-sheet and 24.3\% beta-turn. A theoretical structure model was constructed. The structure from homology modeling is in very good agreement with the crystal structure of mouse Go alpha subunit except for the loop between alpha B-alpha C helices. This model was docked to the mouse RGS16 molecule. T117 on the alpha B-alpha C loop of Go alpha interacted with K172 on RGS16 as opposed to the T117 and K164 interaction in mouse.
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    Molecular modeling and antimycobacterial studies of Mannich bases: 5-hydroxy-2-methyl-4H-pyran-4-ones
    (SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2011-01-01) Berk, Barkin; Us, Demet; Oktem, Sinem; Kocagoz, Z. Tanil; Caglayan, Berrak; Kurnaz, Isil Aksan; Erol, Dilek Demir
    The World Health Organization lists tuberculosis among the top 3 leading causes of death from a single infectious agent, and reported cases of multidrug-resistant tuberculosis (MDR-TB) are on the rise. In an attempt to improve MDR-TB drug-directed therapy, we synthesized 11 4-substituted piperazine derivatives of 3-hydroxy-6-methyl-4H-pyran-4-one pharmacophore by reacting 5-hydroxy-2-methyl-4H-pyran-4-one with suitable piperazine derivatives under Mannich reaction conditions. Inhibitory effects of the 11 compounds on Escherichia coli DNA gyrase were evaluated via DNA gyrase supercoiling assay. The minimum inhibitory concentrations (MIC) of the 11 compounds and 41 compounds from our previous studies against Mycobacterium tuberculosis H37RV were assessed, in vitro, by a broth dilution method. To determine the interaction pattern between active site amino acids and all 52 compounds, homology modeling for the construction of M. tuberculosis DNA gyrase B subunit was performed, followed by a docking study. The data presented here could prove useful in future studies on interaction field analysis and high throughput virtual screening of the derivatives of the 3-hydroxy-6-methyl-4H-pyran-4-one pharmacophore toward the development of more clinically applicable compounds.