A decadentate Gd(III)-coordinating paramagnetic cosolvent for protein relaxation enhancement measurement
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Solvent paramagnetic relaxation enhancement (sPRE) arises from random collisions between paramagnetic cosolvent and protein of interest. The sPRE can be readily measured, affording protein structure information. However, lack of an inert cosolvent probe may yield sPRE values that are not consistent with protein structure. Here we synthesized a new sPRE probe, triethylenetetraamine hexaacetate trimethylamide gadolinium, or Gd(III)–TTHA–TMA. With a total of 10 coordination sites, this paramagnetic cosovlent eliminates an inner-sphere water molecule that can otherwise transfer relaxation to protein through exchange. With the metal ion centered, the new probe is largely spherical with a radius of 4.0 Å, permitting accurate back calculation of sPRE. The effectiveness Gd(III)–TTHA–TMA as a sPRE probe was demonstrated on three well-studied protein systems.
KeywordsNMR spectroscopy Protein structures Paramagnetic relaxation enhancement Paramagnetic probe Solvent PRE
The work was supported by funds from the Ministry of Science and Technology of China (2013CB910200), the National Natural Sciences Foundation of China (21073230, 31170728 and 31125007), and Zhejiang Provincial Natural Science Foundation of China (Z2110059). C.T. is an international early career scientist of Howard Hughes Medical Institute (HHMI).
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