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Christchurch, New Zealand

Lang E.J.M.,Biomolecular Interaction Center | Heyes L.C.,Biomolecular Interaction Center | Jameson G.B.,Massey University | Parker E.J.,University of Canterbury
Journal of the American Chemical Society | Year: 2016

Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include Coulombic interactions, hydrogen bonding, and solvation, as well as backbone motions and side chain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations. To demonstrate the method's validity, we have applied this approach to the subtle dynamic regulation mechanism observed for Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, the first enzyme of aromatic biosynthesis. We were able to identify key communication pathways linking the allosteric binding site to the active site of the enzyme and to validate these findings experimentally by reestablishing the catalytic activity of allosterically inhibited enzyme via modulation of the working pH, without compromising the binding affinity of the allosteric regulator. © 2016 American Chemical Society. Source


Dimartino S.,Biomolecular Interaction Center | Mather A.V.,University of Canterbury | Alestra T.,University of Canterbury | Nawada S.,Biomolecular Interaction Center | Haber M.,Biota Ltd
Interface Focus | Year: 2014

Bioadhesives produced by marine macroalgae represent a potential source of inspiration for the development of water-resistant adhesives. Assessing their adhesion strength, however, remains difficult owing to low volumes of adhesive material produced, low solubility and rapid curing time. These difficulties can be circumvented by testing the adhesion strength of macroalgae propagules attached to a substrate. In this paper, we present a simple, novel flow channel usedtotest the adhesion strength of the germlings of the fucalean alga Hormosira banksiito four substrates of biomedical relevance (PMMA, agar, gelatin and gelatin + lipid). The adhesion strength of H. banksii germlings was found to increase in atime-dependent manner, with minimal adhesion success after a settlement period of 6 h and maximum adhesion strength achieved 24 h after initial settlement. Adhesion success increased most dramatically between 6 and 12 h settlement time, while no additional increase in adhesion strength was recorded for settlement times over 24 h. No significant difference in adhesion strength to the various substrates was observed. Computational fluid dynamics (CFD) was used to estimate the influence of fluid velocity and germling densityon drag force acting on the settled organisms. CFD modelling showed that, on average, the drag force decreased with increasing germling number, suggesting that germlings would benefit from gregarious settlement behaviour. Collectively, our results contribute to a better understanding of the mechanisms allowing benthic marine organisms to thrive in hydrodynamically stressful environments and provide useful insights for further investigations. © 2014 The Author(s) Published by the Royal Society. All rights reserved Source

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