Review of Mutarotase in ‘Metabolic Subculture’ and Analytical Biochemistry: Prelude to 19F NMR Studies of its Substrate Specificity and Mechanism
Dmitry Shishmarev A , Lucas Quiquempoix B , Clément Q. Fontenelle B , Bruno Linclau B and Philip W. Kuchel C DA John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
B School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
C School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
D Corresponding author. Email: philip.kuchel@sydney.edu.au
Dmitry Shishmarev completed his undergraduate degree in chemistry at the Lomonosov Moscow State University in 2009. In 2014, he graduated with a Ph.D. degree in the field of biomolecular NMR spectroscopy under the supervision of Professor Gottfried Otting at the Australian National University. From 2014 to 2017, he worked under the supervision of Professor Philip Kuchel at the University of Sydney to investigate various biophysical properties of red blood cells using NMR. In 2017, he moved back to the Australian National University where he continues his work in biomolecular NMR of proteins and whole cells as an NHMRC Emerging Leadership Fellow. |
Lucas Quiquempoix graduated with a B.Sc. in chemistry from Université de Rouen, France, in 2012. Two years later, he received his Master’s degree in organic chemistry from the same institution after having completed a 6 month placement in Professor Bruno Linclau’s group in Southampton, working on the synthesis of mono- and difluoro-dideoxy glucose analogues. He then joined Professor Linclau’s group as a Ph.D. student to pursue his research on the synthesis of polyfluorinated carbohydrates. He is currently a medicinal chemist for a contract research organisation called Sygnature Discovery based in Nottingham, UK. |
Clément Fontenelle obtained his B.Sc. (2008) and M.Sc. (2010) from Université de Caen-Basse Normandie, France. In 2015, he completed his Ph.D. on the synthesis of polyfluorinated carbohydrates, working in the group of Professor Bruno Linclau at the University of Southampton, UK. After 2 years in the same group, he moved back to Caen in the Laboratoire de Chimie Moléculaire et Thio-organique where he designed the synthesis of fluorinated acyclic nucleoside phosphonates with Professor Thierry Lequeux. He is currently holding a post-doctoral position in the Institut des Molécules et Matériaux du Mans, France, where he works on the PIRAMID project with Professor Anne-Sophie Castanet. |
Professor Bruno Linclau received his Ph.D. from the University of Ghent (Belgium) in 1996. This was followed by a post-doctoral stint with Professor D. P. Curran in Pittsburgh PA (USA), with a fellowship from the Belgian American Educational Foundation. He joined the School of Chemistry at Southampton University in August 1999, and became full Professor in 2015. He is currently Director of Research there. His key research interests are in organofluorine chemistry, in particular how fluorination of aliphatic compounds – including carbohydrates – influences properties such as molecular conformation and lipophilicity, and of hydrogen bond properties of adjacent functional groups. |
Philip Kuchel’s scientific career has been devoted to the application of NMR spectroscopy to the study of cellular systems. Notable discoveries in his group have been the H-bond based ‘split peak effect’, ‘diffusion diffraction’ in red blood cell suspensions, and metabolic- and cation-transport rate dependence on shape changes imposed on red blood cells, mediated by the membrane protein Piezo1. He has been President of the Australian Society for Biophysics, and the Australian Society for Biochemistry and Molecular Biology, and he was elected a Fellow of the Australian Academy of Science in 1997. |
Australian Journal of Chemistry 73(3) 112-116 https://doi.org/10.1071/CH19397
Submitted: 19 August 2019 Accepted: 4 December 2019 Published: 10 February 2020
Abstract
This is the first paper in a sequential pair devoted to the enzyme mutarotase (aldose 1-epimerase; EC 5.1.3.3). Here, the broader context of the physiological role of mutarotase, among those enzymes considered to be part of ‘metabolic structure’, is reviewed. We also summarise the current knowledge about the molecular mechanism and substrate specificity of the enzyme, which is considered in the context of the binding of fluorinated glucose analogues to the enzyme’s active site. This was done as a prelude to our experimental studies of the anomerisation of fluorinated sugars by mutarotase that are described in the following paper.
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