Thermodynamic and kinetic studies of protein structure and enzymic mechanisms

Minton, Allen P.

Abstract

(i) Resonance light scattering is an esoteric technique, which takes advantage of the complex behavior of the refractive index within the absorbance bands of high molecular aggregates of some chromophores. Recently numerous biochemical assays have been published, which claim to use this methodology. We have shown that most of the scattering peaks detected in these experiments are spurious, arising from the properties of the intrument's photomultiplier, not from the molecular species under study. A simple method for the detection of this artifact has been descibed. (McPhie P. 2006) (ii) Antibody presentation is a key step in the initiation of the adaptive immune response, depending on the expression of costimulatory molecules. Immune-enhancing oligodeoxynucleotides (ODNs)increase the expression of these molecules. CD measurements were used to show that several of these regulatory ODNs contain guanine(G)-tetrad structures. Heat treatment of these ODNs which diminishes their regulatory properties also destroyed the G-tetrads. ((Wang J. et al 2007) (iii) Optical studies on the structures of amyloid peptides and proteins are continuing.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIADK024964-03
• Application #: 7967217
• Support Year: 3
• Fiscal Year: 2009
• Total Cost: $362,268

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases

Publications

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

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

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

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

McGlinchey, Ryan P; Shewmaker, Frank; McPhie, Peter et al. (2009) The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis. Proc Natl Acad Sci U S A 106:13731-6