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Looking for Hydrogen Atoms: Neutron Crystallography Provides Novel Insights Into Protein Structure and Function

Emily A. Golden A and Alice Vrielink A B
+ Author Affiliations
- Author Affiliations

A School of Chemistry and Biochemistry, University of Western Australia, Crawley, WA 6009, Australia.

B Corresponding author. Email: alice.vrielink@uwa.edu.au




Emily Golden completed a B.Sc. Honours degree in Biochemistry and Molecular Biology at the University of Western Australia in 2010. In 2011 she began her doctoral studies in Biochemistry, also at the University of Western Australia, under the supervision of Professor Alice Vrielink. Her research interests are in the area of single crystal protein neutron diffraction. She is studying the neutron structure of a flavoenzyme in different redox states in order to gain insights into the redox mechanism of the enzyme.



Professor Alice Vrielink received her B.Sc. (1983) and M.Sc. (1985) in Chemistry from the University of Calgary, Canada. In 1986 she commenced her Ph.D. studies in Biophysics with Professor David Blow at Imperial College London, after being awarded a postgraduate scholarship from the Royal Commission for the Exhibition of 1851. She carried out postdoctoral studies at the Molecular Biology Institute, University of California Los Angeles and at the Imperial Cancer Research Fund, UK. She has held academic positions at McGill University (1994–2000) and the University of California Santa Cruz (2000–2006) before joining the University of Western Australia in 2007 as Professor of Structural Biology. Her research interests focus on using crystallography to study macromolecular structure and function.

Australian Journal of Chemistry 67(12) 1751-1762 https://doi.org/10.1071/CH14337
Submitted: 26 May 2014  Accepted: 8 July 2014   Published: 15 September 2014

Abstract

Neutron crystallography allows direct localization of hydrogen positions in biological macromolecules. Within enzymes, hydrogen atoms play a pivotal role in catalysis. Recent advances in instrumentation and sample preparation have helped to overcome the difficulties of performing neutron diffraction experiments on protein crystals. The application of neutron macromolecular crystallography to a growing number of proteins has yielded novel structural insights. The ability to accurately position water molecules, hydronium ions, and hydrogen atoms within protein structures has helped in the study of low-barrier hydrogen bonds and hydrogen-bonding networks. The determination of protonation states of protein side chains, substrates, and inhibitors in the context of the macromolecule has provided important insights into enzyme chemistry and ligand binding affinities, which can assist in the design of potent therapeutic agents. In this review, we give an overview of the method and highlight advances in knowledge attained through the application of neutron protein crystallography.


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