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A rapid and rational approach to generating isomorphous heavy‐atom phasing derivatives
Author(s) -
Lu Jinghua,
Sun Peter D.
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12910
Subject(s) - derivative (finance) , rational design , phaser , atom (system on chip) , derivatization , chemistry , reactivity (psychology) , metal , peptide , crystal structure , combinatorial chemistry , crystallography , mass spectrometry , stereochemistry , materials science , nanotechnology , organic chemistry , chromatography , computer science , physics , medicine , biochemistry , alternative medicine , pathology , financial economics , optics , economics , embedded system
In attempts to replace the conventional trial‐and‐error heavy‐atom derivative search method with a rational approach, we previously defined heavy metal compound reactivity against peptide ligands. Here, we assembled a composite pH ‐ and buffer‐dependent peptide reactivity profile for each heavy metal compound to guide rational heavy‐atom derivative search. When knowledge of the best‐reacting heavy‐atom compound is combined with mass spectrometry assisted derivatization, and with a quick‐soak method to optimize phasing, it is likely that the traditional heavy‐atom compounds could meet the demand of modern high‐throughput X‐ray crystallography. As an example, we applied this rational heavy‐atom phasing approach to determine a previously unknown mouse serum amyloid A2 crystal structure.