- Title
- Slipknot or Crystallographic Error: A Computational Analysis of the Plasmodium falciparum DHFR Structural Folds
- Creator
- Tata, Rolland B, Alsulami, Ali F, Sheik Amamuddy, Olivier, Blundell, Tom L, Tastan Bishop, Özlem
- Subject
- To be catalogued
- Date
- 2022
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/476115
- Identifier
- vital:77883
- Identifier
- https://doi.org/10.3390/ijms23031514
- Description
- The presence of protein structures with atypical folds in the Protein Data Bank (PDB) is rare and may result from naturally occurring knots or crystallographic errors. Proper characterisation of such folds is imperative to understanding the basis of naturally existing knots and correcting crystallographic errors. If left uncorrected, such errors can frustrate downstream experiments that depend on the structures containing them. An atypical fold has been identified in P. falciparum dihydrofolate reductase (PfDHFR) between residues 20–51 (loop 1) and residues 191–205 (loop 2). This enzyme is key to drug discovery efforts in the parasite, necessitating a thorough characterisation of these folds. Using multiple sequence alignments (MSA), a unique insert was identified in loop 1 that exacerbates the appearance of the atypical fold-giving it a slipknot-like topology. However, PfDHFR has not been deposited in the knotted proteins database, and processing its structure failed to identify any knots within its folds. The application of protein homology modelling and molecular dynamics simulations on the DHFR domain of P. falciparum and those of two other organisms (E. coli and M. tuberculosis) that were used as molecular replacement templates in solving the PfDHFR structure revealed plausible unentangled or open conformations of these loops. These results will serve as guides for crystallographic experiments to provide further insights into the atypical folds identified.
- Format
- 15 pages, pdf
- Language
- English
- Relation
- International Journal of Molecular Sciences, Tata, R. B., Alsulami, A. F., Sheik Amamuddy, O., Blundell, T. L., and Tastan Bishop, Ö. (2022). Slipknot or Crystallographic Error: A Computational Analysis of the Plasmodium falciparum DHFR Structural Folds. International Journal of Molecular Sciences, 23(3), 1514. https://doi.org/10.3390/ijms23031514, International Journal of Molecular Sciences volume 23 number 1514 2022 1422-0067
- Rights
- Author
- Rights
- Use of this resource is governed by the terms and conditions of the Creative Commons CC BY-NC-ND 4.0 License (Attribution-NonCommercial-NoDerivatives 4.0 International) https://creativecommons.org/licenses/by-nc-nd/4.0/
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Sheik Amamuddy, Olivier (Dr)
Tastan Bishop, Ozlem (Prof)
SDG 03. Good Health and Well-Being
RU Department of Biochemistry, Microbiology and Bioinformatics
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details | SOURCE1 | Slipknot or Crystallographic Error A Computational Analysis of the Plasmodium falciparum DHFR Structural Folds.pdf | 6 MB | Adobe Acrobat PDF | View Details |