Research Article: An overview of heavy-atom derivatization of protein crystals

Date Published: March 01, 2016

Publisher: International Union of Crystallography

Author(s): Ashley C. W. Pike, Elspeth F. Garman, Tobias Krojer, Frank von Delft, Elisabeth P. Carpenter.


This review summarizes the reasons why the heavy-atom derivatization of protein crystals can be useful, how to select heavy atoms, how to produce a heavy-atom-modified crystal that still diffracts and how to determine whether the protein has been modified.

Partial Text

Some proteins are born with heavy atoms (selenomethionine labelling), some achieve heavy atoms (cofactors or intrinsic metal ions) and some have heavy atoms thrust upon them (heavy-atom labelling)(with apologies to W. Shakespeare).

HAs are useful because of their ability to bind to proteins, and indeed many HA compounds can attach to a range of biological molecules, including DNA. However, this property also makes most of them highly toxic to humans and many other organisms. They can be carcinogenic, teratogenic (damaging to the unborn child) and highly toxic on inhalation or on contact with skin.

Heavy-atom derivatization remains a useful tool for phasing protein structures, particularly in cases where there are no known homologous structures, where there are large changes in conformation and/or the resolution is low or the chain trace is in doubt. It is not necessarily the first method to try when phasing a structure, but it is, and will continue to be, a very valuable way to obtain phase information for macromolecular structure determination.




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