Conformationally locked lanthanide chelating tags for convenient pseudocontact shift protein nuclear magnetic resonance spectroscopy

Joss, Daniel and Walliser, Roché M. and Zimmermann, Kaspar and Häussinger, Daniel. (2018) Conformationally locked lanthanide chelating tags for convenient pseudocontact shift protein nuclear magnetic resonance spectroscopy. Journal of Biomolecular NMR, 72 (1-2). pp. 29-38.

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Official URL: https://edoc.unibas.ch/68485/

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Pseudocontact shifts (PCS) generated by lanthanide chelating tags yield valuable restraints for investigating protein structures, dynamics and interactions in solution. In this work, dysprosium-, thulium- and terbium-complexes of eight-fold methylated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid tags [DOTA-M8-(4R4S)-SSPy] are presented that induce large pseudocontact shifts up to 5.5 ppm and adopt exclusively the square antiprismatic conformation. This is in contrast to our earlier findings on complexes of the stereoisomeric DOTA-M8-(8S)-SSPy, where significant amounts of the twisted square antiprismatic conformer for the Dy tag were observed. The Dy-, Tm-, Tb- and Lu-complexes of DOTA-M8-(4R4S)-SSPy were conjugated to ubiquitin S57C and selectively; 15; N leucine labeled human carbonic anhydrase II S50C, resulting in only one set of signals. Furthermore, we investigated the conformation of the thulium- and dysprosium-complexes in vacuo and with implicit water solvent using density functional theory calculations. The calculated energy differences between the two different conformations (7.0-50.5 kJ/mol) and experimental evidence from the corresponding ytterbium- and yttrium-complexes clearly suggest a SAP [Λ(δδδδ)] geometry for the complexes presented in this study. The lanthanide chelating tag studied in this work offer insights into the solution structure of proteins by inducing strong pseudocontact shifts, show different tensor properties compared to its predecessor, enables a convenient assignment procedure, is accessed by a more economic synthesis than its predecessor and constitutes a highly promising starting point for further developments of lanthanide chelating tags.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Nuclear Magnetic Resonance (Häussinger)
UniBasel Contributors:Häussinger, Daniel and Joss, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:18 Jun 2019 13:23
Deposited On:18 Jun 2019 13:23

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