Galactokinase catalyses the first committed step of the Leloir pathway, i.e. the ATP-dependent phosphorylation of α-D-galactose at C1-OH. Reduced galactokinase activity results in the inherited metabolic disease type II galactosaemia. However, inhibition of galactokinase is considered a viable approach to treating more severe forms of galactosaemia (types I and III). Considerable progress has been made in the identification of high affinity, selective inhibitors. Although the structure of galactokinase from a variety of species is known, its catalytic mechanism remains uncertain. Although the bulk of evidence suggests that the reaction proceeds via an active site base mechanism, some experimental and theoretical studies contradict this. The enzyme has potential as a biocatalyst in the production of sugar 1-phosphates. This potential is limited by its high specificity. A variety of approaches have been taken to identify galactokinase variants which are more promiscuous. These have broadened galactokinase's specificity to include a wide range of D- and L-sugars. Initial studies suggest that some of these alterations result in increased flexibility at the active site. It is suggested that modulation of protein flexibility is at least as important as structural modifications in determining the success or failure of enzyme engineering.
Skip Nav Destination
Article navigation
February 2016
-
Cover Image
Cover Image
Scanning electron micrograph of a cell from the endosperm of a barley grain. The cell is tightly packed with large, disk-shaped (A-type) and much smaller, almost spherical (B-type) starch granules. The smooth areas in this image are the surface of the cell walls of neighbouring endosperm cells. For further details see pp. 157-163. Image kindly provided by Elaine Barclay and Vasilios Andriotis (John Innes Centre, Norwich). - PDF Icon PDF LinkTable of Contents
Review Article|
February 09 2016
Galactokinase promiscuity: a question of flexibility?
Megan McAuley;
Megan McAuley
*School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL. U.K.
Search for other works by this author on:
Helena Kristiansson;
Helena Kristiansson
1
*School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL. U.K.
Search for other works by this author on:
Meilan Huang;
Meilan Huang
†School of Chemistry and Chemical Engineering, Queen's University, Belfast, David Kier Building, Stranmillis Road, Belfast BT9 5AG. U.K.
Search for other works by this author on:
Angel L. Pey;
Angel L. Pey
‡Department of Physical Chemistry, Faculty of Sciences, University of Granada, Av. Fuentenueva s/n, Granada 18071, Spain
Search for other works by this author on:
David J. Timson
David J. Timson
2
*School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL. U.K.
§School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton BN2 4GJ, U.K.
2To whom correspondence should be addressed (email d.timson@brighton.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 09 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (1): 116–122.
Article history
Received:
November 09 2015
Citation
Megan McAuley, Helena Kristiansson, Meilan Huang, Angel L. Pey, David J. Timson; Galactokinase promiscuity: a question of flexibility?. Biochem Soc Trans 15 February 2016; 44 (1): 116–122. doi: https://doi.org/10.1042/BST20150188
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.