Journal article
Use of cyclic peptides to induce crystallization – case study with prolyl hydroxylase domain 2
- Abstract:
- Crystallization is the bottleneck in macromolecular crystallography; even when a protein crystallises, crystal packing often influences ligand-binding and protein–protein interaction interfaces, which are the key points of interest for functional and drug discovery studies. The human hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) readily crystallises as a homotrimer, but with a sterically blocked active site. We explored strategies aimed at altering PHD2 crystal packing by protein modification and molecules that bind at its active site and elsewhere. Following the observation that, despite weak inhibition/binding in solution, succinamic acid derivatives readily enable PHD2 crystallization, we explored methods to induce crystallization without active site binding. Cyclic peptides obtained via mRNA display bind PHD2 tightly away from the active site. They efficiently enable PHD2 crystallization in different forms, both with/without substrates, apparently by promoting oligomerization involving binding to the C-terminal region. Although our work involves a specific case study, together with those of others, the results suggest that mRNA display-derived cyclic peptides may be useful in challenging protein crystallization cases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 3.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-020-76307-8
Authors
- Publisher:
- Nature Research
- Journal:
- Scientific Reports More from this journal
- Volume:
- 10
- Issue:
- 2020
- Article number:
- 21964
- Publication date:
- 2020-12-15
- Acceptance date:
- 2020-10-26
- DOI:
- EISSN:
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2045-2322
- Language:
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English
- Keywords:
- Pubs id:
-
1139987
- Local pid:
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pubs:1139987
- Deposit date:
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2020-10-27
Terms of use
- Copyright holder:
- Chowdhury et al.
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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