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Human cannabinoid receptor type 1 (hCB1R) plays important roles in the regulation of appetite and development of addictive behaviors. Herein, we describe the design, synthesis, photocharacterization, molecular docking, and in vitro characterization of "photo-rimonabant", i.e., azo-derivatives of the selective hCB1R antagonist SR1411716A (rimonabant...
The Front Cover shows a covalent inhibitor (orange) simultaneously addressing the active sites of the Chlamydia trachomatis deubiquitylase 1 (Cdu1, green) and the adenovirus protease (adenain, red). The covalent bond is highlighted in yellow. The structural similarities of evolutionarily related proteases have been successfully harnessed for the re...
Based on the similarity between the active sites of the deubiquitylating and deneddylating enzyme ChlaDub1 (Cdu1) and the evolutionary related protease adenain a target‐hopping approach screening on a focused set of adenain inhibitors has been pursued. The thereby identified cyano‐pyrimidine based inhibitors represent the first active‐site directed...
Raw data for quantitative analysis of C. trachomatis Cdu1-FLAG infectivity, Mcl-1 stabilization and apoptosis inhibition shown in Figure 3—figure supplement 2.DOI: http://dx.doi.org/10.7554/eLife.21465.013
Raw data for quantitative analysis of Mcl-1 ring intensity around C. trachomatis pTet/Cdu1 inclusions uninduced and induced for Cdu1 overexpression shown in Figure 6—figure supplement 2.DOI: http://dx.doi.org/10.7554/eLife.21465.025
Raw data for quantitative analysis of Mcl-1 stabilization, Mcl-1-ringed inclusion count and calculation of Mcl-1 ring intensity of HeLa cells infected with C. trachomatis wild type and Tn-cdu1 shown in Figure 6.DOI: http://dx.doi.org/10.7554/eLife.21465.022
Plasmids. Listed are all plasmids used in this study to transfect human cells or to transform E. coli or C. trachomatis. If not stated otherwise, constructs were cloned in this study using the oligo nucleotides listed in Supplementary file 4. DOI: http://dx.doi.org/10.7554/eLife.21465.035
Chlamydia trachomatis strains. Listed are all C. trachomatis strains used and generated in this study. All C. trachomatis strains generated by transformation and selection originate from the C. trachomatis LGV L2 (434) (ATCC VR-902B) strain. DOI: http://dx.doi.org/10.7554/eLife.21465.036
Data collection and refinement statistics. X-ray crystallographic data collection and refinement statistics for the structure of Cdu1 (155-401). Data for the highest resolution shell are given in parentheses. a: Firedel’s mates were kept separately for calculation. DOI: http://dx.doi.org/10.7554/eLife.21465.034
Oligo nucleotides. Listed are all oligo nucleotides in 5’ → 3’ orientation used in this study. The oligo nucleotides were used for construct cloning, sequencing or southern hybridization as indicated in the comment column. DOI: http://dx.doi.org/10.7554/eLife.21465.037
Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of th...