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Karsten Niefind   Professor  Senior Scientist or Principal Investigator 
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Karsten Niefind published an article in March 2019.
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0 crystal structure
Top co-authors See all
Andrew Abell

124 shared publications

ARC Centre of Excellence for Nanoscale Biophotonics, Institute for Photonics and Advanced Sensing, School of Physical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia

Joachim Jose

115 shared publications

Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany

Marc Le Borgne

94 shared publications

E Faculté de Pharmacie-ISPB, Department of Bioactive Molecules and Medicinal Chemistry , Université de Lyon, Université Claude Bernard Lyon 1 , Lyon , France

Werner Hummel

59 shared publications

Faculty of Chemistry; Bielefeld University; Universitätsstr. 25 33615 Bielefeld Germany

Claudia Götz

51 shared publications

Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany

75
Publications
18
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0
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416
Citations
Publication Record
Distribution of Articles published per year 
(1999 - 2019)
Total number of journals
published in
 
22
 
Publications See all
Article 0 Reads 0 Citations Diacritic Binding of an Indenoindole Inhibitor by CK2α Paralogs Explored by a Reliable Path to Atomic Resolution CK2α′ S... Dirk Lindenblatt, Anna Nickelsen, Violetta M. Applegate, Jen... Published: 19 March 2019
ACS Omega, doi: 10.1021/acsomega.8b03415
DOI See at publisher website
Article 0 Reads 0 Citations Design of CK2β‐Mimicking Peptides as Tools To Study the CK2α/CK2β Interaction in Cancer Cells Dirk Lindenblatt, Mareike Horn, Claudia Götz, Karsten Niefin... Published: 12 March 2019
ChemMedChem, doi: 10.1002/cmdc.201800786
DOI See at publisher website PubMed View at PubMed
Article 3 Reads 0 Citations Crystal structure of highly glycosylated human leukocyte elastase in complex with an S2′ site binding inhibitor Jennifer Hochscherf, Markus Pietsch, William Tieu, Kevin Kua... Published: 26 July 2018
Acta Crystallographica Section F Structural Biology Communications, doi: 10.1107/s2053230x1800537x
DOI See at publisher website
PREPRINT-CONTENT 6 Reads 1 Citation An EDS1 EP-domain surface mediating timely transcriptional reprogramming of immunity genes Deepak Dharamchand Bhandari, Dmitry Lapin, Barbara Kracher, ... Published: 05 July 2018
Plant Biology, doi: 10.1101/362921
DOI See at publisher website ABS Show/hide abstract
Plant intracellular NLR receptors recognize pathogen interference to trigger immunity. NLR signalling mechanisms have not been resolved. Enhanced disease susceptibility1 (EDS1) heterodimers are recruited by Toll-interleukin1-receptor domain NLRs (TNLs) to transcriptionally mobilize resistance pathways. Using an Arabidopsis EDS1 heterodimer crystal structure we interrogate the conserved but functionally uncharacterized EDS1 α-helical EP-domain. We identify EP-domain positively charged residues lining a cavity that are essential for TNL immunity signalling, beyond heterodimer formation. Mutating arginine (R493) to alanine creates a weak EDS1 allele which disables TNL immunity against bacteria producing a virulence factor, coronatine (COR). Arabidopsis plants expressing EDS1R493A are slow to mobilize defence gene expression changes, independently of COR. The transcriptional delay has severe consequences for pathogen resistance and for countering bacterial COR. We uncover a set of host immunity genes whose repression by COR is blocked by wild-type EDS1 but not by EDS1R493A in the TNL response. These data uncover an EDS1 signalling surface lining the heterodimer EP-domain cavity which confers timely transcriptional reprogramming of host defence pathways and blocks bacterial virulence in NLR receptor immunity.
Article 0 Reads 0 Citations Improved protein-crystal identification by using 2,2,2-trichloroethanol as a fluorescence enhancer Christian Pichlo, Christine Toelzer, Konrad Chojnacki, Sinan... Published: 24 April 2018
Acta Crystallographica Section F Structural Biology Communications, doi: 10.1107/s2053230x18005253
DOI See at publisher website
Article 7 Reads 0 Citations A π-Halogen Bond of Dibenzofuranones with the Gatekeeper Phe113 in Human Protein Kinase CK2 Leads to Potent Tight Bindin... Alexander Schnitzler, Andreas Gratz, Andre Bollacke, Michael... Published: 17 February 2018
Pharmaceuticals, doi: 10.3390/ph11010023
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Human protein kinase CK2 is an emerging target for neoplastic diseases. Potent lead structures for human CK2 inhibitors are derived from dibenzofuranones. Two new derivatives, 7,9-dichloro-1,2-dihydro-8-hydroxy-4-[(4-methoxyphenylamino)-methylene]dibenzo[b,d]furan-3(2H)-one (4a) and (E)-1,3-dichloro-6-[(4-methoxyphenylimino)-methyl]dibenzo[b,d]furan-2,7-diol (5) were tested for inhibition of CK2 and induction of apoptosis in LNCaP cells. Both turned out to be tight binding inhibitors, with IC50 values of 7 nM (4a) and 5 nM (5) and an apparent Ki value of 0.4 nM for both. Compounds 4a and 5 reduced cellular CK2 activity, indicating cell permeability. Cell viability was substantially impaired in LNCaP cells, as well as apoptosis was induced, which was not appearing in non-neoplastic ARPE-19 cells. Co-crystallization of 4a and 5 revealed an unexpected π-halogen bond of the chloro substituent at C9 with the gatekeeper amino acid Phe113, leading to an inverted binding mode in comparison to parent compound 4b, with the Cl at C6 instead, which was co-crystallized as a control. This indicates that the position of the chloro substituent on ring A of the dibenzofuran scaffold is responsible for an inversion of the binding mode that enhances potency.
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