Standard Article

Macromolecules, X-Ray Diffraction of Biological

  1. Albrecht Messerschmidt,
  2. Robert Huber

Published Online: 15 SEP 2006

DOI: 10.1002/3527600906.mcb.200400058

Encyclopedia of Molecular Cell Biology and Molecular Medicine

Encyclopedia of Molecular Cell Biology and Molecular Medicine

How to Cite

Messerschmidt, A. and Huber, R. 2006. Macromolecules, X-Ray Diffraction of Biological. Encyclopedia of Molecular Cell Biology and Molecular Medicine. .

Author Information

  1. Max-Planck-Institut für Biochemie, Martinsried, Germany

Publication History

  1. Published Online: 15 SEP 2006


X-ray diffraction of biomolecules covers diffraction experiments on single crystals of small biological molecules such as oligopeptides, cofactors, steroid hormones, and so on, or biological macromolecules. But it also includes small angle scattering experiments on biological macromolecules in solution. This chapter is exclusively dedicated to the X-ray crystallography of biological macromolecules. It comprises the determination of the three-dimensional structures of proteins, nucleic acids, and other biological macromolecules at atomic resolution by diffraction of X-rays on crystals of such macromolecules. The atomic structure is obtained from the electron density distribution of the macromolecular crystal, which is the Fourier transform of the waves diffracted by the crystal. The amplitudes of the diffracted waves are determined directly from the diffraction experiment. The diffraction phases are revealed (1) from additional diffraction data of isomorphous heavy atom derivatives (multiple isomorphous replacement (MIR) technique), (2) from multiple anomalous diffraction (MAD), if suitable anomalous scatterers are in the crystal and using tunable synchrotron radiation, and (3) by Patterson search techniques (molecular replacement), if structural information on the biological macromolecule under investigation is available. X-ray crystallography of biological macromolecules is the unique method for the elucidation of the spatial structures at atomic resolution of complex biomolecules with molecular masses greater than 30 kDa. The structures represent a time and spatial average of molecules packed in a crystal. The preparation of suitable crystals may be a limiting factor.


  • Anomalous scattering;
  • Atomic scattering factor;
  • Crystallographic R-factor;
  • Electron density function;
  • Ewald construction;
  • MAD;
  • MIR;
  • Phase problem;
  • Reciprocal lattice;
  • Resolution;
  • Structure factor