Abstract
Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2,4-pentanediol (MPD) separately using the R and S enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozyme and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization.
Highlights
IntroductionAccording to the most recently available statistics from the Structural Biology Knowledgebase (Gabanyi et al, 2011), fewer than one in eight purified proteins produces diffraction-quality crystals
We examined the effect of water solvation on the relative conformer energies at the same level of quantum-chemical theory, incorporating the default integral equation formalism variant (IEF) within the polarizable continuum model (PCM) for placing a solute in a cavity within the solvent reaction field (SCRF; Tomasi et al, 2005)
We examined the ( 1, 2) conformations of (R)- and (S)-MPD found in the Protein Data Bank (PDB) (Berman et al, 2000)
Summary
According to the most recently available statistics from the Structural Biology Knowledgebase (Gabanyi et al, 2011), fewer than one in eight purified proteins produces diffraction-quality crystals. This success rate has been decreasing over the past decade (Chayen, 2002, 2004; Chayen & Saridakis, 2008); one explanation offered is that the proteins which are easy to crystallize were tackled first (Pusey et al, 2005). These additives are typically salts, small organic molecules and polymers (Dumetz et al, 2009; McPherson et al, 2011), other additives have been used, such as silicon-based surfaces that promote nucleation (Chayen et al, 2001; Ghatak & Ghatak, 2011; Tsekova et al, 2012)
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