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Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution (2024)
Journal Article
Scott, D. J., & Winzor, D. J. (in press). Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution. European Biophysics Journal, https://doi.org/10.1007/s00249-024-01722-y

This communication summarizes findings from the earliest encounters with extreme enthalpy‒entropy compensation, a phenomenon first detected in the 1950s by a reappraisal of isopiestic and calorimetric measurements on aqueous urea solutions in terms o... Read More about Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution.

Multiplexing projects: supervising undergraduate research projects with larger cohorts (2024)
Journal Article
Nisbet, E., Scott, D., & Campeotto, I. (in press). Multiplexing projects: supervising undergraduate research projects with larger cohorts. The Biochemist,

Almost all undergraduate students in the UK complete a final year research project or dissertation. In the molecular biosciences field, these projects are often based in individual research laboratory. However, with increasing student numbers, fallin... Read More about Multiplexing projects: supervising undergraduate research projects with larger cohorts.

Is there reversible dimerization of albumin in blood plasma? And does it matter? (2024)
Journal Article
Harris, G., Bradshaw, M. L., Halsall, D. J., Scott, D. J., Unwin, R. J., & Norden, A. G. W. (2024). Is there reversible dimerization of albumin in blood plasma? And does it matter?. Experimental Physiology, 109(10), 1663-1671. https://doi.org/10.1113/EP092012

Most albumin in blood plasma is thought to be monomeric with some 5% covalently dimerized. However, many reports in the recent biophysics literature find that albumin is reversibly dimerized or even oligomerized. We review data on this from X‐ray cry... Read More about Is there reversible dimerization of albumin in blood plasma? And does it matter?.

The adaptability of the ion binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF (2023)
Journal Article
Lithgo, R. M., Hanževački, M., Harris, G., Kamps, J. J. .. G., Holden, E., Gianga, T., …Scott, D. J. (2023). The adaptability of the ion binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF. Journal of Biological Chemistry, 299(11), Article 105331. https://doi.org/10.1016/j.jbc.2023.105331

The periplasmic chaperone SilF has been identified as part of an Ag(I) detoxification system in Gram negative bacteria. Sil proteins also bind Cu(I), but with reported weaker affinity, therefore leading to the designation of a specific detoxification... Read More about The adaptability of the ion binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF.

eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation (2023)
Journal Article
Schmidt, T., Dabrowska, A., Waldron, J. A., Hodge, K., Koulouras, G., Gabrielsen, M., …Bushell, M. (2023). eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. Nucleic Acids Research, 51(4), 1859-1879. https://doi.org/10.1093/nar/gkad030

Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root of oncogenic translational programmes. It remains unclear how these mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate thei... Read More about eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation.

Quantifying the concentration dependence of sedimentation coefficients for globular macromolecules: a continuing age-old problem (2021)
Journal Article
Winzor, D. J., Dinu, V., Scott, D. J., & Harding, S. E. (2021). Quantifying the concentration dependence of sedimentation coefficients for globular macromolecules: a continuing age-old problem. Biophysical Reviews, 13(2), 273-288. https://doi.org/10.1007/s12551-021-00793-x

This retrospective investigation has established that the early theoretical attempts to directly incorporate the consequences of radial dilution into expressions for variation of the sedimentation coefficient as a function of the loading concentratio... Read More about Quantifying the concentration dependence of sedimentation coefficients for globular macromolecules: a continuing age-old problem.

Use of molecular crowding for the detection of protein self-association by size-exclusion chromatography (2019)
Journal Article
Mrozowich, T., Winzor, D. J., Scott, D. J., & Patel, T. R. (2019). Use of molecular crowding for the detection of protein self-association by size-exclusion chromatography. Analytical Biochemistry, 584, Article 113392. https://doi.org/10.1016/j.ab.2019.113392

The feasibility of employing molecular crowding cosolutes to facilitate the detection of protein self-association by zonal size exclusion chromatography is investigated. Theoretical considerations have established that although the cosolute-induced d... Read More about Use of molecular crowding for the detection of protein self-association by size-exclusion chromatography.

The carbonic anhydrase of Clostridium autoethanogenum represents a new subclass of β-carbonic anhydrases (2019)
Journal Article
Pander, B., Harris, G., Scott, D. J., Winzer, K., Köpke, M., Simpson, S. D., …Henstra, A. M. (2019). The carbonic anhydrase of Clostridium autoethanogenum represents a new subclass of β-carbonic anhydrases. Applied Microbiology and Biotechnology, 103(17), 7275-7286. https://doi.org/10.1007/s00253-019-10015-w

Carbonic anhydrase catalyses the interconversion of carbon dioxide and water to bicarbonate and protons. It was unknown if the industrial relevant acetogen Clostridium autoethanogenum possesses these enzymes. We identified two putative carbonic anhyd... Read More about The carbonic anhydrase of Clostridium autoethanogenum represents a new subclass of β-carbonic anhydrases.

Structural modeling of an outer membrane electron conduit from a metal-reducing bacterium suggests electron transfer via periplasmic redox partners (2018)
Journal Article
Edwards, M. J., White, G. F., Lockwood, C. W., Lawes, M. C., Martel, A., Harris, G., …Clarke, T. A. (2018). Structural modeling of an outer membrane electron conduit from a metal-reducing bacterium suggests electron transfer via periplasmic redox partners. Journal of Biological Chemistry, 293(21), 8103-8112. https://doi.org/10.1074/jbc.RA118.001850

Many subsurface microorganisms couple their metabolism to the reduction or oxidation of extracellular substrates. For example, anaerobic mineral-respiring bacteria can use external metal oxides as terminal electron acceptors during respiration. Porin... Read More about Structural modeling of an outer membrane electron conduit from a metal-reducing bacterium suggests electron transfer via periplasmic redox partners.

Allowance for boundary sharpening in the determination of diffusion coefficients by sedimentation velocity: a historical perspective. (2018)
Journal Article

This review summarizes endeavors undertaken in the middle of last century to employ the Lamm equation for quantitative analysis of boundary spreading in sedimentation velocity experiments on globular proteins, thereby illustrating the ingenuity requi... Read More about Allowance for boundary sharpening in the determination of diffusion coefficients by sedimentation velocity: a historical perspective..

Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA (2017)
Journal Article
Hyde, E. I., Callow, P., Rajasekar, K. V., Timmins, P., Patel, T. P., Siligardi, G., …Scott, D. J. (2017). Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA. Biochemical Journal, 474(18), 3121-3135. https://doi.org/10.1042/BCJ20170281

© 2017 The Author(s). The ParB protein, KorB, from the RK2 plasmid is required for DNA partitioning and transcriptional repression. It acts co-operatively with other proteins, including the repressor KorA. Like many multifunctional proteins, KorB con... Read More about Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA.

Accounting for thermodynamic non-ideality in the Guinier region of small-angle scattering data of proteins (2016)
Journal Article
Scott, D. J. (2016). Accounting for thermodynamic non-ideality in the Guinier region of small-angle scattering data of proteins. Biophysical Reviews, 8(4), https://doi.org/10.1007/s12551-016-0235-5

Hydrodynamic studies of the solution properties of proteins and other biological macromolecules are often hard to interpret when the sample is present at a reasonably concentrated solution. The reason for this is that solutions exhibit deviations fro... Read More about Accounting for thermodynamic non-ideality in the Guinier region of small-angle scattering data of proteins.

STAT2 is a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways (2016)
Journal Article
Ho, J., Pelzel, C., Begitt, A., Mee, M., Elsheikha, H. M., Scott, D. J., & Vinkemeier, U. (2016). STAT2 is a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways. PLoS Biology, 14(10), 1-27. https://doi.org/10.1371/journal.pbio.2000117

STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IF... Read More about STAT2 is a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways.

Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS) (2016)
Journal Article
Perkins, S. J., Wright, D. W., Zhang, H., Brookes, E. H., Chen, J., Irving, T. C., …Curtis, J. E. (2016). Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS). Journal of Applied Crystallography, 49(6), 1861-1875. https://doi.org/10.1107/S160057671601517X

The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallog... Read More about Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS).

Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator (2016)
Journal Article
Bingle, L. E., Rajasekar, K. V., Lovering, A. L., Dancea, F., Scott, D. J., Harris, S. A., …White, S. A. (2016). Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator. Nucleic Acids Research, 44(10), 4947-4956. https://doi.org/10.1093/nar/gkw191

The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, Ko... Read More about Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator.

Comparison of the Structure and Activity of Glycosylated and Aglycosylated Human Carboxylesterase 1 (2015)
Journal Article
Arena de Souza, V., Scott, D. J., Nettleship, J. E., Rahman, N., Charlton, M. H., Walsh, M. A., & Owens, R. J. (2015). Comparison of the Structure and Activity of Glycosylated and Aglycosylated Human Carboxylesterase 1. PLoS ONE, 10(12), e0143919. https://doi.org/10.1371/journal.pone.0143919

Human Carboxylesterase 1 (hCES1) is the key liver microsomal enzyme responsible for detoxification and metabolism of a variety of clinical drugs. To analyse the role of the single N-linked glycan on the structure and activity of the enzyme, authentic... Read More about Comparison of the Structure and Activity of Glycosylated and Aglycosylated Human Carboxylesterase 1.

Evaluation of diffusion coefficients by means of an approximate steady-state condition in sedimentation velocity distributions (2015)
Journal Article
Scott, D. J., Harding, S. E., & Winzor, D. J. (2015). Evaluation of diffusion coefficients by means of an approximate steady-state condition in sedimentation velocity distributions. Analytical Biochemistry, 490, https://doi.org/10.1016/j.ab.2015.08.017

This investigation examined the feasibility of manipulating the rotor speed in sedimentation velocity experiments to spontaneously generate an approximate steady-state condition where the extent of diffusional spreading is matched exactly by the boun... Read More about Evaluation of diffusion coefficients by means of an approximate steady-state condition in sedimentation velocity distributions.

Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian pPeptide transport (2015)
Journal Article
Beale, J. H., Parker, J. L., Samsudin, F., Barrett, A. L., Senan, A., Bird, L. E., …Newstead, S. (2015). Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian pPeptide transport. Structure, 23(10), https://doi.org/10.1016/j.str.2015.07.016

Mammals obtain nitrogen via the uptake of di- and tri-peptides in the gastrointestinal tract through the action of PepT1 and PepT2, which are members of the POT family of proton-coupled oligopeptide transporters. PepT1 and PepT2 also play an importan... Read More about Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian pPeptide transport.

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation (2015)
Journal Article
Langowski, J., Zhao, H., Ghirlando, R., Alfonso, C., Arisaka, F., Attali, I., …Schuck, P. (2015). A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation. PLoS ONE, 10(5), Article e0126420. https://doi.org/10.1371/journal.pone.0126420

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose o... Read More about A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation.