Cryptochromes (CRYs) are evolutionarily conserved photoreceptors that mediate various light-induced responses in bacteria, plants, and animals. Plant cryptochromes govern a variety of critical growth and developmental processes including seed germination, flowering time and entrainment of the circadian clock. CRY’s photocycle involves reduction of their flavin adenine dinucleotide (FAD)-bound chromophore, which is completely oxidized in the dark and semi to fully reduced in the light signaling-active state. Despite the progress in characterizing cryptochromes, important aspects of their photochemistry, regulation, and light-induced structural changes remain to be addressed. In this study, we determine the crystal structure of the photosensory domain of Arabidopsis CRY2 in a tetrameric active state. Systematic structure-based analyses of photo-activated and inactive plant CRYs elucidate distinct structural elements and critical residues that dynamically partake in photo-induced oligomerization. Our study offers an updated model of CRYs photoactivation mechanism as well as the mode of its regulation by interacting proteins.

The nociceptin receptor (NOPR) is an orphan G protein-coupled receptor that contains seven transmembrane helices. NOPR has a distinct mechanism of activation, though it shares a significant homology with other opioid receptors. Previously there have been reports on homology modeling of NOPR and also molecular dynamics simulation studies for a short period. Recently the crystal structure of NOPR was reported. In this study, we analyzed the time dependent behavior of NOPR docked with clinically important agonist molecules such as NOP (natural agonist) peptide and compound 10 (SCH-221510 derivative) using molecular dynamics simulations (MDS) for 100 ns. Molecular dynamics simulations of NOPR-agonist complexes allowed us to refine the system and to also identify stable structures with better binding modes. Structure activity relationships (SAR) for SCH221510 derivatives were investigated and reasons for the activities of these derivatives were determined. Our molecular dynamics trajectory analysis of NOPR-peptide and NOPR-compound 10 complexes found residues to be crucial for binding. Mutagenesis studies on the residues identified from our analysis could prove useful. Our results could also provide useful information in the structure-based drug design of novel and potent agonists targeting NOPR.

Cryptochromes (CRYs) are evolutionarily conserved blue-light receptors that mediate various light-induced responses in bacteria, plants, and animals. Plant cryptochromes govern a variety of critical growth and developmental processes including seed germination, flowering time and entrainment of the circadian clock. CRYs photocycle involves reduction of their flavin adenine dinucleotide (FAD)-bound chromophore, which is completely oxidized in the dark and semireduced in the light signalling-active state. Despite the significant progress in characterizing cryptochromes, important aspects of their photochemistry, regulation, and light-induced structural adaptation remain to be addressed. In this study, we determine the crystal structure of the photosensory domain of Arabidopsis CRY2 in a tetrameric active state. Systematic structurebased analyses of photo-activated and inactive plant CRYs elucidate new structural elements and critical residues that dynamically partake in photo-induced oligomerization. Our study offers an updated model of CRYs photoactivation mechanism as well as the mode of its regulation by interacting proteins.

No abstract

Key indicators: single-crystal X-ray study; T = 293 K; mean (C-C) = 0.003 Å; R factor = 0.063; wR factor = 0.190; data-to-parameter ratio = 25.7.In the title compound, C 26 H 22 N 2 O 3 , the pyrrolidine ring adopts an envelope conformation with the N atom as the flap. In the crystal, pairs of centrosymmetrically related molecules are linked into dimers by N-HÁ Á ÁO hydrogen bonds. In addition, there are C-HÁ Á ÁO hydrogen bonds. Related literature ExperimentalCrystal data