Premium
Simplified heavy‐atom derivatization of protein structures via co‐crystallization with the MAD tetragon tetrabromoterephthalic acid
Author(s) -
Truong Jia Q.,
Nguyen Stephanie,
Bruning John B.,
Shearwin Keith E.
Publication year - 2021
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x21004052
Subject(s) - phaser , crystallization , protein crystallization , crystallography , crystal structure , macromolecule , molecular replacement , phase problem , chemistry , materials science , diffraction , physics , optics , organic chemistry , biochemistry
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.