The phase problem is a persistent bottleneck that impedes the structure‐determination pipeline and must be solved to obtain atomic resolution crystal structures of macromolecules. Although molecular replacement has become the predominant method of s...
The phase problem is a persistent bottleneck that impedes the structure‐determination pipeline and must be solved to obtain atomic resolution crystal structures of macromolecules. Although molecular replacement has become the predominant method of solving the phase problem, many scenarios still exist in which experimental phasing is needed. Here, a proof‐of‐concept study is presented that shows the efficacy of using tetrabromoterephthalic acid (B4C) as an experimental phasing compound. Incorporating B4C into the crystal lattice using co‐crystallization, the crystal structure of hen egg‐white lysozyme was solved using MAD phasing. The strong anomalous signal generated by its four Br atoms coupled with its compatibility with commonly used crystallization reagents render B4C an effective experimental phasing compound that can be used to overcome the phase problem.
Tetrabromoterephthalic acid (B4C) provides sufficient anomalous signal to solve the crystal structure of hen egg‐white lysozyme using MAD phasing. The use of B4C as an experimental phasing compound offers several advantages over existing compounds, including its compatibility with common crystallization reagents and its amenability to co‐crystallization.