Hochdurchsatz-Kristallisationseinheit
Zusammenfassung der Projektergebnisse
1. The structure biology of photo-reception as well as cell wall and membrane architecture: (i.) Photoreceptors, including phytochromes, cryptochromes, and photolyases that are responsible for signal transduction concerning the plant growth, gene expression, tuning the circadian clock and in case for the photolyases, DNA-repair. (ii.) The structure-activity relationship of mitochondrial membrane voltage-dependent anion channels (VDAC) a key player during the apoptotic process. (iii.) Fungal adhesin superfamily of proteins. 2. Structural elucidation of Fe-S protein biogenesis in eukaryotes: Iron–sulphur (Fe–S) clusters are essential and versatile cofactors of proteins involved in catalysis, electron transport and sensing of ambient conditions. Defects in Fe–S protein biogenesis leads to severe diseases (e.g. cerebral ataxia, anaemia). There are about 20 proteins and protein-protein complexes in this process structurally studied that includes the inner-mitochondrial membrane ABC transporter, Atm1. 3. Structure-based drug design by exploring the structural basis of ligand–protein interaction by X-ray crystallography: Proteins investigated include Factor XIII, HIV-1 protease, tRNA-guanine transglycosylase and thrombin. The crystal structures are the basis for further ligand optimization to obtain highly specific inhibitors with affinities in the nanomolar range. 4. Proteins, which affect the pathogenicity of Shigella sp., the causative agent of bacillary dysentery: OspD1, Spa15 and IpgC are involved in the regulation of the "late" Shigella pathogenicity genes. The project involves understanding the regulation at a structural level, which may, in a longer term, enable us to design small molecules as a means to fight Shigellosis. 5. Understanding enzyme mechanisms for structure-based drug design: Two enzymes are in the current focus of research: (i.) Human aldose reductase; (ii.) Carbonic anhydrases. Both are involved in important physiological and pathological processes including pH homeostasis, bicarbonate metabolism, regulation of intracellular osmotic pressure, biosynthetic reactions (e.g. gluconeogenesis), bone resorption, calcification and tumorgenicity. We are studying sulfonamide/sulfamide inhibitor complexes at high resolution to understand detailed protein–ligand interactions. 6. The structural biology of bacterial macromolecular complexes (e.g. the bacterial flagellum, divisome): The current projects are: (i.) Nucleotide-binding proteins and their accessory factors; (ii.) Components of the flagellar type 3 secretion system (T3SS); (iii.) Factors, which regulate transcription and translation of subunits during assembly of the bacterial flagellum/divisome; (iv.) Alarmone (i.e. (p)ppGpp) producing enzyme complexes; (v.) Flagellum-associated proteins with a role in biofilm formation.
Projektbezogene Publikationen (Auswahl)
- Crystal structures of an archaeal class II DNA photolyase and its complex with UV- damaged duplex DNA. EMBO Journal, vol.30, p.4437-4449, 2011
Kiontke S., Geisselbrecht Y., Pokorny R., Carell T., Batschauer A., Essen L.O.
- Spectroscopy and a high-resolution crystal structure of Tyr263 mutants of cyanobacterial phytochrome Cph1. J Mol Biol. 2011 Oct 14;413(1):115-27
Mailliet J, Psakis G, Feilke K, Sineshchekov V, Essen LO, Hughes J
(Siehe online unter https://doi.org/10.1016/j.jmb.2011.08.023) - Flexibility of the N-terminal mVDAC1 segment controls the channel's gating behavior. PLoS One. 2012;7(10):e47938
Mertins B, Psakis G, Grosse W, Back KC, Salisowski A, Reiss P, Koert U, Essen LO
(Siehe online unter https://doi.org/10.1371/journal.pone.0047938) - Structural analysis of coniferyl alcohol 9-O-methyltransferase from Linum nodiflorum reveals a novel active-site environment. Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):888-900
Wolters S, Neeb M, Berim A, Schulze Wischeler J, Petersen M, Heine A
(Siehe online unter https://doi.org/10.1107/S0907444913002874) - Structure of active coagulation factor XIII triggered by calcium binding: basis for the design of next-generation anticoagulants. Angew Chem Int Ed Engl. 2013 Nov 4;52(45):11930-4
Stieler M, Weber J, Hils M, Kolb P, Heine A, Büchold C, Pasternack R, Klebe G
(Siehe online unter https://doi.org/10.1002/anie.201305133) - Structure of the cyanobacterial phytochrome 2 photosensor implies a tryptophan switch for phytochrome signaling. Journal of Biological Chemistry, vol.288, p.35714-35725, 2013
Anders K., Daminelli-Widany G., Mroginski M.A., von Stetten D., Essen L.O.
- Structural and evolutionary aspects of antenna chromophore usage by class II photolyases. J Biol Chem. 2014 Jul 11;289(28):19659-69
Kiontke S, Gnau P, Haselsberger R, Batschauer A, Essen LO
(Siehe online unter https://doi.org/10.1074/jbc.M113.542431) - Structural basis for HTLV-1 protease inhibition by the HIV-1 protease inhibitor indinavir. J Med Chem. 2014 Jul 24;57(14):6266-72
Kuhnert M, Steuber H, Diederich WE
(Siehe online unter https://doi.org/10.1021/jm500402c) - Xanthomonins I-III: a new class of lasso peptides with a seven-residue macrolactam ring. Angew Chem Int Ed Engl. 2014 Feb 17; 53(8):2230-4
Hegemann JD1, Zimmermann M, Zhu S, Steuber H, Harms K, Xie X, Marahiel MA
(Siehe online unter https://doi.org/10.1002/anie.201309267) - Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16864-9
Maestre-Reyna M, Diderrich R, Veelders MS, Eulenburg G, Kalugin V, Brückner S, Keller P, Rupp S, Mösch HU, Essen LO
(Siehe online unter https://doi.org/10.1073/pnas.1207653109)
