An investigation into structural changes due to deuteration

Fisher, S.J.; Helliwell, John R.

doi:10.1107/s0108767308004807

Cited by 43 publications

(28 citation statements)

References 37 publications

(15 reference statements)

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“…These results further validate the increasingly widespread use of perdeuteration in neutron crystallography 10. It should be noted that while the two structures look identical at the resolution obtained, atomic resolution data (≤1 Å)11 may help to further clarify the small structural effects associated with H/D isotopic replacement 12…”

supporting

confidence: 66%

Impact of Deuteration on the Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidoses

Yee

Moulin

Breteau³

et al. 2016

Angew Chem Int Ed

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It is well established that the formation of transthyretin (TTR) amyloid fibrils is linked to the destabilization and dissociation of its tetrameric structure into insoluble aggregates. Isotope labeling is used for the study of TTR by NMR, neutron diffraction, and mass spectrometry (MS). Here MS, thioflavin T fluorescence, and crystallographic data demonstrate that while the X‐ray structures of unlabeled and deuterium‐labeled TTR are essentially identical, subunit exchange kinetics and amyloid formation are accelerated for the deuterated protein. However, a slower subunit exchange is noted in deuterated solvent, reflecting the poorer solubility of non‐polar protein side chains in such an environment. These observations are important for the interpretation of kinetic studies involving deuteration. The destabilizing effects of TTR deuteration are rather similar in character to those observed for aggressive mutations of TTR such as L55P (associated with familial amyloid polyneuropathy).

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supporting

confidence: 66%

Impact of Deuteration on the Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidoses

Yee

Moulin

Breteau³

et al. 2016

Angew Chem Int Ed

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“…The SIE involves the structure of water and macromolecules. On the other hand, the DIE involves the ability of D 2 8,32) . Although it is not easy to distinguish between the SIE and DIE, long-term effects are probably due to the DIE and short-term effects to the SIE.…”

Section: Original Articlementioning

confidence: 99%

Effects of Deuterium Oxide on Streptococcus mutans and Pseudomonas aeruginosa

Hirai

Tomida

Kikuchi

et al. 2010

Bull. Tokyo Dent. Coll.

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A complex aggregation of microorganisms growing on a solid substrate is termed a biofilm and is considered to be an etiological agents. Pseudomonas aeruginosa and Streptococcus mutans are representative bacteria in such biofilms. It is well known that deuterium oxide (D 2 O) causes toxic effects on a number of biological systems. We investigated the effects of D 2 O on growth and biofilm formation of P. aeruginosa and S. mutans. These bacteria were incubated in medium containing D 2 O (100%, 75% or 0%) at 37°C for 24hr, 48 hr or 72hr. Growth of P. aeruginosa was inhibited by D 2 O within the first 48hr. However, after 72 hr, growth rate was seen to increase in the D 2 O-containing medium compared with in medium without D 2 O. In contrast, the growth of S. mutans in the D 2 O medium was inhibited within 72hr. The biofilm formation of P. aeruginosa was increased in the D 2 O medium. Biofilm formation of S. mutans in the D 2 O medium increased compared with in the medium without D 2 O, but this increase was only temporary in the case of P. aeruginosa. Compared to biofilm formation in 0% D 2 O medium marked as 100%, the biofilm formation rate of S. mutans in 75% D 2 O medium was 143% at 24hr, 146% at 48 hr and 130% at 72 hr. In other D 2 O concentration media biofilm formation was lower. In 100% D 2 O medium, biofilm formation rate decreased from 114% at 24hr to 56% at 72hr. The biofilm formation rate of P. aeruginosa in 100% D 2 O medium was 172% at 24hr, but decreased to 88% at 72hr. Biofilm formation of P. aeruginosa in 75% and 0% D 2 O media showed no significant difference. We consider that these results were due to stress or alteration in bacterial metabolisms.

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“…We conclude from this comparative study that perdeuteration does not affect the protein or the solvent structure in the case of DFPase. A review of the literature shows that perdeuteration has no significant effect on overall structure in small molecules and proteins (Fisher & Helliwell, 2008), although in the case of haloalkane dehalogenase differences in the crystallization pH led to a number of conformational changes in the active site (Liu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

X-ray structure of perdeuterated diisopropyl fluorophosphatase (DFPase): perdeuteration of proteins for neutron diffraction

Blum¹,

Tomanicek

John

et al. 2010

Acta Cryst Sect F

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PDB Reference: perdeuterated diisopropyl fluorophosphatase, 3kgg.The signal-to-noise ratio is one of the limiting factors in neutron macromolecular crystallography. Protein perdeuteration, which replaces all H atoms with deuterium, is a method of improving the signal-to-noise ratio of neutron crystallography experiments by reducing the incoherent scattering of the hydrogen isotope. Detailed analyses of perdeuterated and hydrogenated structures are necessary in order to evaluate the utility of perdeuterated crystals for neutron diffraction studies. The room-temperature X-ray structure of perdeuterated diisopropyl fluorophosphatase (DFPase) is reported at 2.1 Å resolution. Comparison with an independently refined hydrogenated roomtemperature structure of DFPase revealed no major systematic differences, although the crystals of perdeuterated DFPase did not diffract neutrons. The lack of diffraction is examined with respect to data-collection and crystallographic parameters. The diffraction characteristics of successful neutron structure determinations are presented as a guideline for future neutron diffraction studies of macromolecules. X-ray diffraction to beyond 2.0 Å resolution appears to be a strong predictor of successful neutron structures.

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An investigation into structural changes due to deuteration

Cited by 43 publications

References 37 publications

Impact of Deuteration on the Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidoses

Impact of Deuteration on the Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidoses

Effects of Deuterium Oxide on Streptococcus mutans and Pseudomonas aeruginosa

X-ray structure of perdeuterated diisopropyl fluorophosphatase (DFPase): perdeuteration of proteins for neutron diffraction

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