Projects per year
Glycoside hydrolases, enzymes which cleave glycoside bonds to produce two smaller sugars, are widespread in nature and have correspondingly broad use in biotechnology. Cellulases, glycoside hydrolases that break down cellulose, are used in a broad range of industrial processes, for example clarifying fruit juices, textile processing and a rapidly expanding interest in the possibility of extracting ethanol from waste products of the food industry (stalks, husks etc.) to use as a renewable biofuel.
Thermostability: As part of the Centre for Extremophile Research, I am interested in the structural basis for protein thermostability, comparing proteins from hyperthermophilic organisms to their homologues from organisms growing at room temperature or below.
A recent glycoside hydrolase example is the biotechnologically-important cellulase from Rhodothermus marinus which has a half life of more than 2.5 hours at 90°C, (research in collaboration with Eva Nordberg Karlsson, Lund University). In complex with inhibitors or flash-frozen with substrate, X-ray crystal structures of this cellulase have revealed details of substrate binding mechanisms as well as thermophilic adaptation.
This enzyme shows a number of thermophilic adaptations, the most obvious being a large increase in the number of surface electrostatic interactions (ion pairs) over mesophilic counterparts.
Complementary techniques used to investigate structure and function include X-ray scattering (e.g. for the structure of Rhodothermus marinus xylanase, see the CER pages) and computational analysis. We have used the University of Houston Brownian Dynamics program (UHBD) to quantify the contribution of ion pairs to thermostability of citrate synthase and are testing these predictions in the laboratory by altering the number of ion pairs using site directed mutagenesis.
Pathogenesis: Studies of other glycoside hydrolases such as cell-wall-degrading enzymes secreted by Stagonospora nodorum, a wheat pathogen, understanding of which will aid disease control (in collaboration with Prof Richard Cooper) and enzymes with potential for intervention in human disease (in collaboration with Dr Andrew Watts, Pharmacy & Pharmacology) are at a less advanced stage.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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An Integrated Approach to Explore a Novel Paradigm for Biofuel Production from Lignocellulosic Feedstocks
1/03/17 → 31/03/22
Project: Research council
Staphylococcal complement evasion protein Sbi stabilises C3d dimers by inducing an N-terminal helix swapDunphy, R., Wahid, A., Back, C., Martin, B., Watts, A., Dodson, C., Crennell, S. & Van Den Elsen, J., 25 May 2022, In: Frontiers in Immunology. 13, 892234.
Research output: Contribution to journal › Article › peer-reviewOpen Access1 Citation (SciVal)8 Downloads (Pure)
Structurally Informed Mutagenesis of a Stereochemically Promiscuous Aldolase Produces Mutants That Catalyze the Diastereoselective Syntheses of All Four Stereoisomers of 3Deoxy-hexulosonic AcidRoyer, S. F., Gao, X., Groleau, R., van der Kamp, M. W., Bull, S., Danson, M. J. & Crennell, S., 16 Sept 2022, In: ACS Catalysis. 12, 18, p. 11444-11455 12 p.
Research output: Contribution to journal › Article › peer-reviewOpen Access
Wahid, A., Dunphy, R., Macpherson, A., Gibson, B., Kulik, L., Whale, K., Back, C., Hallam, T., Alkhawaja, B., Martin, B., Meschede, I., Laabei, M., Lawson, A., Holers, V. M., Watts, A., Crennell, S., Harris, C., Marchbank, K. & Van Den Elsen, J., 9 Aug 2021, In: Frontiers in Immunology. 12, 714055.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile2 Citations (SciVal)25 Downloads (Pure)
Macpherson, A., Laabei, M., Ahdash, Z., Graewert, M., Birtley, J., Schulze, M-S., Crennell, S., Robinson, S., Holmes, B., Oleinikovas, V., Nilsson, P., Snowdon, J., Ellis, V., Mollnes, T. E., Deane, C., Svergun, D., Lawson, A. & Van Den Elsen, J., 11 Feb 2021, In: eLife. 10, p. 1-49 49 p., e63586.
Research output: Contribution to journal › Article › peer-reviewOpen Access13 Citations (SciVal)
Structural Stabilisation of Disulphide-Linked Fluid-Phase C3d Dimers by Sbi Suggests a Novel B cell Subversion Strategy by Staphylococcus aureusWahid, A., Dunphy, R., Gibson, B., Back, C., Hallam, T., Alkhawaja, B., Harris, C., Crennell, S., Watts, A., Marchbank, K. & Van Den Elsen, J., Oct 2019, p. 437.
Research output: Contribution to conference › Paper