Outputs (30)

Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases (2018)
Journal Article
Jenner, M., Kosol, S., Griffiths, D., Prasongpholchai, P., Manzi, L., Barrow, A. S., Moses, J. E., Oldham, N. J., Lewandowski, J., & Challis, G. (2018). Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases. Nature Chemical Biology, 14, 270-275. https://doi.org/10.1038/nchembio.2549

Modular polyketide synthases (PKSs) produce numerous structurally complex natural products with diverse applications in medicine and agriculture. They typically consist of several multienzyme subunits that utilize structurally-defined docking domains... Read More about Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases.

Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane-Spanning Protein (2017)
Journal Article
Manzi, L., Barrow, A. S., Hopper, J. T., Kaminska, R., Kleanthous, C., Robinson, C. V., Moses, J. E., & Oldham, N. J. (2017). Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane-Spanning Protein. Angewandte Chemie International Edition, 56(47), 14873-14877. https://doi.org/10.1002/anie.201708254

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Mapping the interaction sites between membrane-spanning proteins is a key challenge in structural biology. In this study a carbene-footprinting approach was developed and applied to identify the in... Read More about Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane-Spanning Protein.

A front-face 'SNi synthase' engineered from a retaining 'double-SN2' hydrolase (2017)
Journal Article
Iglesias-Fernández, J., Hancock, S. M., Lee, S. S., Khan, M., Kirkpatrick, J., Oldham, N. J., McAuley, K., Fordham-Skelton, A., Rovira, C., & Davis, B. G. (2017). A front-face 'SNi synthase' engineered from a retaining 'double-SN2' hydrolase. Nature Chemical Biology, 13, 874-881. https://doi.org/10.1038/nchembio.2394

SNi or SNi-like mechanisms, in which leaving group departure and nucleophile approach occur on the same ‘front’ face, have been observed previously experimentally and computationally in both the chemical and enzymatic (glycosyltransferase) substituti... Read More about A front-face 'SNi synthase' engineered from a retaining 'double-SN2' hydrolase.

Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions (2016)
Journal Article
Manzi, L., Barrow, A. S., Scott, D., Layfield, R., Wright, T. G., Moses, J. E., & Oldham, N. J. (2016). Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions. Nature Communications, 7, Article 13288. https://doi.org/10.1038/ncomms13288

Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods th... Read More about Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions.

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation (2016)
Journal Article
Soukarieh, F., Nowicki, M. W., Bastide, A., Poyry, T., Jones, C., Dudek, K., Patwardhan, G., Meullenet, F., Oldham, N. J., Walkinshaw, M. D., Willis, A. E., & Fischer, P. M. (2016). Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation. European Journal of Medicinal Chemistry, 124, 200-217. https://doi.org/10.1016/j.ejmech.2016.08.047

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 50 - terminal mRNA cap structure (m7 G... Read More about Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.

Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD (2016)
Journal Article
Goode, A., Butler, K., Long, J., Cavey, J., Scott, D., Shaw, B., Sollenberger, J., Gell, C., Johansen, T., Oldham, N. J., Searle, M., & Layfield, R. (2016). Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD. Autophagy, 12(7), 1094-1104. https://doi.org/10.1080/15548627.2016.1170257

Growing evidence implicates impairment of autophagy as a candidate pathogenic mechanism in the spectrum of neurodegenerative disorders which includes amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS-FTLD). SQSTM1, which encode... Read More about Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD.

Acyl hydrolases from trans-AT polyketide synthases target acetyl units on acyl carrier proteins (2016)
Journal Article
Jenner, M., Afonso, J. P., Kohlhaas, C., Karbaum, P., Frank, S., Piel, J., & Oldham, N. J. (in press). Acyl hydrolases from trans-AT polyketide synthases target acetyl units on acyl carrier proteins. Chemical Communications, 52(30), https://doi.org/10.1039/C6CC01453D

Acyl hydrolase (AH) domains are a common feature of trans-AT PKSs. They have been hypothesised to perform a proofreading function by removing acyl chains from stalled sites. This study determines the substrate tolerance of the AH PedC for a range of... Read More about Acyl hydrolases from trans-AT polyketide synthases target acetyl units on acyl carrier proteins.

Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5 (2015)
Journal Article
Scott, D., Layfield, R., & Oldham, N. J. (2015). Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5. Proteomics, 15(16), https://doi.org/10.1002/pmic.201400457

Many proteins exhibit conformation flexibility as part of their biological function, whether through the presence of a series of well-defined states or by the existence of intrinsic disorder. Ion mobility spectrometry, in combination with MS (IM–MS),... Read More about Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5.

Acyl-chain elongation drives ketosynthase substrate selectivity in trans-acyltransferase polyketide synthases (2014)
Journal Article
Jenner, M., Afonso, J. P., Bailey, H. R., Frank, S., Kampa, A., Piel, J., & Oldfield, N. J. (2015). Acyl-chain elongation drives ketosynthase substrate selectivity in trans-acyltransferase polyketide synthases. Angewandte Chemie International Edition, 54(6), https://doi.org/10.1002/anie.201410219

Type I modular polyketide synthases (PKSs), responsible for the biosynthesis of many biologically active agents, possess a ketosynthase (KS) domain within each module to catalyze chain elongation.
Acylation of the KS active site Cys residue is foll... Read More about Acyl-chain elongation drives ketosynthase substrate selectivity in trans-acyltransferase polyketide synthases.

Insights into the structure and assembly of the Bacillus subtilis clamp-loader complex and its interaction with the replicative helicase. (2013)
Journal Article
Afonso, J. P., Chintakayala, K., Suwannachart, C., Sedelnikova, S., Giles, K., Hoyes, J. B., Soultanas, P., Rafferty, J. B., & Oldham, N. J. (2013). Insights into the structure and assembly of the Bacillus subtilis clamp-loader complex and its interaction with the replicative helicase. Nucleic Acids Research, 41(9), https://doi.org/10.1093/nar/gkt173

The clamp-loader complex plays a crucial role in DNA replication by loading the β-clamp onto primed
DNA to be used by the replicative polymerase. Relatively little is known about the stoichiometry,
structure and assembly pathway of this complex, an... Read More about Insights into the structure and assembly of the Bacillus subtilis clamp-loader complex and its interaction with the replicative helicase..