@article{ScheibBroserConstantinetal.2018,
  author    = {Scheib, Ulrike and Broser, Matthias and Constantin, Oana M. and Yang, Shang and Gao, Shiqiang and Mukherjee, Shatanik and Stehfest, Katja and Nagel, Georg and Gee, Christine E. and Hegemann, Peter},
  title     = {Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 {\AA} structure of the adenylyl cyclase domain},
  series = {Nature Communications},
  volume    = {9},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-018-04428-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228517},
  pages     = {2046, 1-15},
  year      = {2018},
  abstract  = {The cyclic nucleotides cAMP and cGMP are important second messengers that orchestrate fundamental cellular responses. Here, we present the characterization of the rhodopsinguanylyl cyclase from Catenaria anguillulae (CaRhGC), which produces cGMP in response to green light with a light to dark activity ratio > 1000. After light excitation the putative signaling state forms with tau = 31 ms and decays with tau = 570 ms. Mutations (up to 6) within the nucleotide binding site generate rhodopsin-adenylyl cyclases (CaRhACs) of which the double mutated YFP-CaRhAC (E497K/C566D) is the most suitable for rapid cAMP production in neurons. Furthermore, the crystal structure of the ligand-bound AC domain (2.25 angstrom) reveals detailed information about the nucleotide binding mode within this recently discovered class of enzyme rhodopsin. Both YFP-CaRhGC and YFP-CaRhAC are favorable optogenetic tools for non-invasive, cell-selective, and spatio-temporally precise modulation of cAMP/cGMP with light.},
  language  = {en}
}
@article{EwaldBartlDandekaretal.2017,
  author    = {Ewald, Jan and Bartl, Martin and Dandekar, Thomas and Kaleta, Christoph},
  title     = {Optimality principles reveal a complex interplay of intermediate toxicity and kinetic efficiency in the regulation of prokaryotic metabolism},
  series = {PLOS Computational Biology},
  volume    = {13},
  journal   = {PLOS Computational Biology},
  number    = {2},
  doi       = {10.1371/journal.pcbi.1005371},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180870},
  pages     = {19},
  year      = {2017},
  abstract  = {A precise and rapid adjustment of fluxes through metabolic pathways is crucial for organisms to prevail in changing environmental conditions. Based on this reasoning, many guiding principles that govern the evolution of metabolic networks and their regulation have been uncovered. To this end, methods from dynamic optimization are ideally suited since they allow to uncover optimality principles behind the regulation of metabolic networks. We used dynamic optimization to investigate the influence of toxic intermediates in connection with the efficiency of enzymes on the regulation of a linear metabolic pathway. Our results predict that transcriptional regulation favors the control of highly efficient enzymes with less toxic upstream intermediates to reduce accumulation of toxic downstream intermediates. We show that the derived optimality principles hold by the analysis of the interplay between intermediate toxicity and pathway regulation in the metabolic pathways of over 5000 sequenced prokaryotes. Moreover, using the lipopolysaccharide biosynthesis in Escherichia coli as an example, we show how knowledge about the relation of regulation, kinetic efficiency and intermediate toxicity can be used to identify drug targets, which control endogenous toxic metabolites and prevent microbial growth. Beyond prokaryotes, we discuss the potential of our findings for the development of antifungal drugs.},
  language  = {en}
}