Issue 11, 2017

Principles and methods used to grow and optimize crystals of protein–metallodrug adducts, to determine metal binding sites and to assign metal ligands

Abstract

The characterization of the interactions between biological macromolecules (proteins and nucleic acids) and metal-based drugs is a fundamental prerequisite for understanding their mechanisms of action. X-ray crystallography enables the structural analysis of such complexes with atomic level detail. However, this approach requires the preparation of highly diffracting single crystals, the measurement of diffraction patterns and the structural analysis and interpretation of macromolecule–metal interactions from electron density maps. In this review, we describe principles and methods used to grow and optimize crystals of protein–metallodrug adducts, to determine metal binding sites and to assign and validate metal ligands. Examples from the literature and experience in our own laboratory are provided and key challenges are described, notably crystallization and molecular model refinement against the X-ray diffraction data.

Graphical abstract: Principles and methods used to grow and optimize crystals of protein–metallodrug adducts, to determine metal binding sites and to assign metal ligands

Article information

Article type
Tutorial Review
Submitted
27 ⵢⵓⵍ 2017
Accepted
06 ⵛⵓⵜ 2017
First published
20 ⵛⵓⵜ 2017

Metallomics, 2017,9, 1534-1547

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