TY - JOUR
T1 - A complement to the modern crystallographer's toolbox
T2 - caged gadolinium complexes with versatile binding modes
AU - Stelter, Meike
AU - Molina, Rafael
AU - Jeudy, Sandra
AU - Kahn, Richard
AU - Abergel, Chantal
AU - Hermoso, Juan A
PY - 2014/6
Y1 - 2014/6
N2 - A set of seven caged gadolinium complexes were used as vectors for introducing the chelated Gd(3+) ion into protein crystals in order to provide strong anomalous scattering for de novo phasing. The complexes contained multidentate ligand molecules with different functional groups to provide a panel of possible interactions with the protein. An exhaustive crystallographic analysis showed them to be nondisruptive to the diffraction quality of the prepared derivative crystals, and as many as 50% of the derivatives allowed the determination of accurate phases, leading to high-quality experimental electron-density maps. At least two successful derivatives were identified for all tested proteins. Structure refinement showed that the complexes bind to the protein surface or solvent-accessible cavities, involving hydrogen bonds, electrostatic and CH-π interactions, explaining their versatile binding modes. Their high phasing power, complementary binding modes and ease of use make them highly suitable as a heavy-atom screen for high-throughput de novo structure determination, in combination with the SAD method. They can also provide a reliable tool for the development of new methods such as serial femtosecond crystallography.
AB - A set of seven caged gadolinium complexes were used as vectors for introducing the chelated Gd(3+) ion into protein crystals in order to provide strong anomalous scattering for de novo phasing. The complexes contained multidentate ligand molecules with different functional groups to provide a panel of possible interactions with the protein. An exhaustive crystallographic analysis showed them to be nondisruptive to the diffraction quality of the prepared derivative crystals, and as many as 50% of the derivatives allowed the determination of accurate phases, leading to high-quality experimental electron-density maps. At least two successful derivatives were identified for all tested proteins. Structure refinement showed that the complexes bind to the protein surface or solvent-accessible cavities, involving hydrogen bonds, electrostatic and CH-π interactions, explaining their versatile binding modes. Their high phasing power, complementary binding modes and ease of use make them highly suitable as a heavy-atom screen for high-throughput de novo structure determination, in combination with the SAD method. They can also provide a reliable tool for the development of new methods such as serial femtosecond crystallography.
KW - Binding Sites
KW - Crystallography, X-Ray/methods
KW - Gadolinium/chemistry
KW - Molecular Structure
U2 - 10.1107/S1399004714005483
DO - 10.1107/S1399004714005483
M3 - Journal article
C2 - 24914962
SN - 2059-7983
VL - 70
SP - 1506
EP - 1516
JO - Acta crystallographica. Section D, Biological crystallography
JF - Acta crystallographica. Section D, Biological crystallography
IS - Pt 6
ER -