A complement to the modern crystallographer's toolbox: caged gadolinium complexes with versatile binding modes

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 -