Associate Professor Shaun Lott
BSc (Hons), PhD
1994 University of Leeds, UK, PhD, Biochemistry and Molecular Biology
1990 University of Surrey, UK, BSc (1st Class Honours), Biochemistry
Research | Current
I am interested in using structural analysis and a range of biochemical and biophysical tools to address important biological systems. Current projects in the lab include:
These toxins are composed of three core subunits (A, B and C) and are best characterised from insect pathogens such as Yersinia entomophaga. Jason Busby has determined the first structure of the BC sub-complex, work that was recently published in Nature (Busby et al. 2013). Together with the structure of the A subunit previously determined by electron microscopy (Landsberg et al. 2011) and the structures of the associated chitinase enzymes (Busby et al. 2012), this gives us the first complete picture of this class of toxin. We are now working to produce engineered versions of the complex. This is a collaboration with Mark Hurst at AgResearch and Michael Landsberg at the University of Queensland.
Non-ribosomal peptides synthases
Non-ribosomal peptide synthases (NRPSs) are large modular enzymes that produce an extensive range of secondary metabolites in bacteria and fungi. Verne Lee determined the structure of an adenylation domain from the endophytic fungus Neotyphodium lolii, the first fungal structure to be determined (Lee et al. 2010). He is now investigating the structure and function of the first archaeal NRPS enzyme to be identified.
Proteins from Mycobacterium tuberculosis known to be essential for pathogenesis
The tryptophan biosynthetic pathway is essential for M. tuberculosis to cause disease, and may also have a role in the interaction of the bacterium with the host immune system. We have determined the structures of the enzymes that catalyse the first two steps in tryptophan biosynthesis, and have developed inhibitors against them (Castell et al. 2013). This work has been carried out by Dr Genevieve Evans in collaboration with Prof Bill Denny.
The regulation of cholesterol metabolism
We are also working on the regulation of cholesterol metabolism by the transcriptional regulators KstR and KstR2. This work is an ongoing collaboration with Sharon Kendall at the Royal Veterinary College in London and Lindsay Eltis at the University of British Columbia.
Teaching | Current
- Recipient of 2006 Queenstown Molecular Biology/Invitrogen Life Science Award
Areas of expertise
- Structural Biology
- Bacterial pathogenesis
Selected publications and creative works (Research Outputs)
- Rechiche, O., Plowman, J. E., Harland, D. P., Lee, T. V., & Lott, J. S. (2018). Expression and purification of high sulfur and high glycine-tyrosine keratin-associated proteins (KAPs) for biochemical and biophysical characterization. Protein expression and purification, 146, 34-44. 10.1016/j.pep.2017.12.006
Other University of Auckland co-authors: Othman RECHICHE, Verne Lee
- Evans, G. L., Furkert, D. P., Abermil, N., Kundu, P., de Lange, K. M., Parker, E. J., ... Lott, J. S. (2018). Anthranilate phosphoribosyltransferase: Binding determinants for 5'-phospho-alpha-d-ribosyl-1'-pyrophosphate (PRPP) and the implications for inhibitor design. Biochimica et Biophysica Acta - Proteins and Proteomics, 1866 (2), 264-274. 10.1016/j.bbapap.2017.08.018
Other University of Auckland co-authors: Daniel Furkert, Edward Baker, Margaret Brimble
- Evans, G. L., Furkert, D. P., Abermil, N., Kundu, P., de Lange, K. M., Parker, E. J., ... Lott, J. S. (2017). Datasets, processing and refinement details for Mtb-AnPRT: inhibitor structures with various space groups. Data in brief, 15, 1019-1029. 10.1016/j.dib.2017.10.051
Other University of Auckland co-authors: Daniel Furkert, Edward Baker
- Gerth, M. L., Liu, Y., Jiao, W., Zhang, X.-X., Baker, E. N., Lott, J. S., ... Johnston, J. M. (2017). Crystal structure of a bicupin protein HutD involved in histidine utilization in Pseudomonas. Proteins, 85 (8), 1580-1588. 10.1002/prot.25303
Other University of Auckland co-authors: Jodie Johnston, Edward Baker
- Lott, J. S., & Lee, T. V. (2017). Revealing the inter-module interactions of multi-modular nonribosomal peptide synthetases. Structure, 25 (5), 693-695. 10.1016/j.str.2017.04.003
Other University of Auckland co-authors: Verne Lee
- Lott, J. S. (2017). Tryptophan Biosynthesis in Bacteria: Drug Targets and Immunology. In D'Mello JPF (Ed.) (pp. 267-276). CABI PUBLISHING-C A B INT.
- Ho, N. A. T., Dawes, S. S., Crowe, A. M., Casabon, I., Gao, C., Kendall, S. L., ... Lott, J. S. (2016). The structure of the transcriptional repressor KstR in complex with CoA thioester cholesterol metabolites sheds light on the regulation of cholesterol catabolism in Mycobacterium tuberculosis. Journal of Biological Chemistry, 291 (14), 7256-7266. 10.1074/jbc.M115.707760
Other University of Auckland co-authors: Stephanie Dawes, Edward Baker
- Busby, J. N., Lott, J. S., & Panjikar, S. (2016). Combining cross-crystal averaging and MRSAD to phase a 4354-amino-acid structure. Acta crystallographica. Section D, Structural biology, 72 (Pt 2), 182-191. 10.1107/s2059798315023566
Other University of Auckland co-authors: Jason Busby