TY  - JOUR
A1  - Dietschreit, Johannes C. B.
A1  - Wagner, Annika
A1  - Le, T. Anh
A1  - Klein, Philipp
A1  - Schindelin, Hermann
A1  - Opatz, Till
A1  - Engels, Bernd
A1  - Hellmich, Ute A.
A1  - Ochsenfeld, Christian
T1  - Predicting \(^{19}\)F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex
JF  - Angewandte Chemie International Edition
N2  - The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable \(^{19}\)F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the \(^{19}\)F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of \(^{19}\)F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area.
KW  - African sleeping sickness
KW  - covalent inhibitors
KW  - NMR spectroscopy
KW  - quantum chemistry
KW  - structural biology
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214879
VL  - 59
IS  - 31
SP  - 12669
EP  - 12673
ER  - 
TY  - JOUR
A1  - Binas, Oliver
A1  - Bessi, Irene
A1  - Schwalbe, Harald
T1  - Structure Validation of G‐Rich RNAs in Noncoding Regions of the Human Genome
JF  - ChemBioChem
N2  - We present the rapid biophysical characterization of six previously reported putative G‐quadruplex‐forming RNAs from the 5′‐untranslated region (5′‐UTR) of silvestrol‐sensitive transcripts for investigation of their secondary structures. By NMR and CD spectroscopic analysis, we found that only a single sequence—[AGG]\(_{2}\)[CGG]\(_{2}\)C—folds into a single well‐defined G‐quadruplex structure. Sequences with longer poly‐G strands form unspecific aggregates, whereas CGG‐repeat‐containing sequences exhibit a temperature‐dependent equilibrium between a hairpin and a G‐quadruplex structure. The applied experimental strategy is fast and provides robust readout for G‐quadruplex‐forming capacities of RNA oligomers.
KW  - biophysical investigation
KW  - circular dichroism
KW  - G-quadruplexes
KW  - NMR spectroscopy
KW  - RNA
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214892
VL  - 21
IS  - 11
SP  - 1656
EP  - 1663
ER  - 
TY  - JOUR
A1  - Mueller, Thomas D.
A1  - Fiebig, Juliane E.
A1  - Weidauer, Stella E.
A1  - Qiu, Li-Yan
A1  - Bauer, Markus
A1  - Schmieder, Peter
A1  - Beerbaum, Monika
A1  - Zhang, Jin-Li
A1  - Oschkinat, Hartmut
A1  - Sebald, Walter
T1  - The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed
JF  - Molecules
N2  - Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop.
KW  - bone morphogenetic proteins
KW  - TGF-β superfamily
KW  - BMP antagonist
KW  - protein-protein recognition
KW  - NMR spectroscopy
KW  - von Willebrand type C domain
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97196
ER  -