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Racemic crystallography of synthetic protein enantiomers used to determine the X‐ray structure of plectasin by direct methods
Author(s) -
Mandal Kalyaneswar,
Pentelute Brad L.,
Tereshko Valentina,
Thammavongsa Vilasak,
Schneewind Olaf,
Kossiakoff Anthony A.,
Kent Stephen B. H.
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.127
Subject(s) - chemistry , enantiomer , crystal structure , dimer , crystallization , molecule , crystallography , x ray crystallography , racemic mixture , stereochemistry , x ray , diffraction , organic chemistry , physics , optics , quantum mechanics
We describe the use of racemic crystallography to determine the X‐ray structure of the natural product plectasin, a potent antimicrobial protein recently isolated from fungus. The protein enantiomers L ‐plectasin and D ‐plectasin were prepared by total chemical synthesis; interestingly, L ‐plectasin showed the expected antimicrobial activity, while D ‐plectasin was devoid of such activity. The mirror image proteins were then used for racemic crystallization. Synchrotron X‐ray diffraction data were collected to atomic resolution from a racemic plectasin crystal; the racemate crystallized in the achiral centrosymmetric space group P 1 with one L ‐plectasin molecule and one D ‐plectasin molecule forming the unit cell. Dimer‐like intermolecular interactions between the protein enantiomers were observed, which may account for the observed extremely low solvent content (13%–15%) and more highly ordered nature of the racemic crystals. The structure of the plectasin molecule was well defined for all 40 amino acids and was generally similar to the previously determined NMR structure, suggesting minimal impact of the crystal packing on the plectasin conformation.