(i) Optical studies on the structures of amyloid peptides and proteins are continuing.We are particularly interested in origin of the very intense CD spectrum which has been associated with the cross-beta structure of amyloid fibrils. This phenomenon is shown by peptides which have been shown to form amyloid with both parallel and anti-parallel beta sheet structure. (ii) In collaboration with the group of T. K. Dayie and B. Chen (Univ. of MD), we have investigated the effect of a small inert cosolute, trimethylamine oxide (TMAO), on the conformational changes of the SAM II riboswitch in the presence of increasing concentrations of the metabolite S-adenosyl-methionine (SAM) and Mg++. The free riboswitch was thought to be in an open or semi-random conformation in the absence of SAM and Mg++ and to become more folded and compact upon binding SAM and/or Mg++. Extensive measurements of the dependence of circular dichroism spectra of the riboswitch upon the concentrations of these small ligands may be quantitatively accounted for by a model, according to which SAM binds exclusively to a compact conformation. In the absence of SAM, the riboswitch seems to be a mixture of open and compact states. Low concentrations of Mg++ or TMAO bind to the open form(s), inhibiting the binding of SAM. At higher concentrations, cooperative binding of Mg++ or molecular crowding by TMAO, transform the riboswitch into the compact form, facilitating the binding of SAM. Further binding of Mg++ increases the affinity of the compact form of the riboswitch for SAM. Hydrodynamic measurements show that the riboswitch is compacted by concentrated TMAO. (iii) Optical studies on the structure of carbon nanotubes.

Project Start
Project End
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Budget End
Support Year
9
Fiscal Year
2015
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
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McPhie, Peter; Brown, Patrick; Chen, Bin et al. (2016) Modulation of Conformational Equilibria in the S-Adenosylmethionine (SAM) II Riboswitch by SAM, Mg(2+), and Trimethylamine N-Oxide. Biochemistry 55:5010-20
Chagas, Andrezza C; McPhie, Peter; San, Hong et al. (2014) Simplagrin, a platelet aggregation inhibitor from Simulium nigrimanum salivary glands specifically binds to the Von Willebrand factor receptor in collagen and inhibits carotid thrombus formation in vivo. PLoS Negl Trop Dis 8:e2947
Backus, Keriann M; Dolan, Michael A; Barry, Conor S et al. (2014) The three Mycobacterium tuberculosis antigen 85 isoforms have unique substrates and activities determined by non-active site regions. J Biol Chem 289:25041-53
Zhang, Min; Khripin, Constantine Y; Fagan, Jeffrey A et al. (2014) Single-step total fractionation of single-wall carbon nanotubes by countercurrent chromatography. Anal Chem 86:3980-4
Chattopadhyay, Manas K; Fernandez, Cristina; Sharma, Deepak et al. (2011) Yeast ornithine decarboxylase and antizyme form a 1:1 complex in vitro: purification and characterization of the inhibitory complex. Biochem Biophys Res Commun 406:177-82
McGlinchey, Ryan P; Shewmaker, Frank; Hu, Kan-nian et al. (2011) Repeat domains of melanosome matrix protein Pmel17 orthologs form amyloid fibrils at the acidic melanosomal pH. J Biol Chem 286:8385-93
Calvo, Eric; Tokumasu, Fuyuki; Mizurini, Daniella M et al. (2010) Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo. FEBS J 277:413-27
Phillips, Robert S; Miles, Edith W; McPhie, Peter et al. (2010) Effects of hydrostatic pressure on the conformational equilibrium of tryptophan synthase from Salmonella typhimurium. Ann N Y Acad Sci 1189:95-103
Shewmaker, Frank; McGlinchey, Ryan P; Thurber, Kent R et al. (2009) The functional curli amyloid is not based on in-register parallel beta-sheet structure. J Biol Chem 284:25065-76
Fernandez, Cristina; Minton, Allen P (2009) Static light scattering from concentrated protein solutions II: experimental test of theory for protein mixtures and weakly self-associating proteins. Biophys J 96:1992-8

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