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Identification of allosteric disulfides from labile bonds in X-ray structures
Protein disulfide bonds link pairs of cysteine sulfur atoms and are either structural or functional motifs. The allosteric disulfides control the function of the protein in which they reside when cleaved or formed. Here, we identify potential allosteric disulfides in all Protein Data Bank X-ray stru...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society Publishing
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830721/ https://www.ncbi.nlm.nih.gov/pubmed/29515832 http://dx.doi.org/10.1098/rsos.171058 |
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author | Pijning, Aster E. Chiu, Joyce Yeo, Reichelle X. Wong, Jason W. H. Hogg, Philip J. |
author_facet | Pijning, Aster E. Chiu, Joyce Yeo, Reichelle X. Wong, Jason W. H. Hogg, Philip J. |
author_sort | Pijning, Aster E. |
collection | PubMed |
description | Protein disulfide bonds link pairs of cysteine sulfur atoms and are either structural or functional motifs. The allosteric disulfides control the function of the protein in which they reside when cleaved or formed. Here, we identify potential allosteric disulfides in all Protein Data Bank X-ray structures from bonds that are present in some molecules of a protein crystal but absent in others, or present in some structures of a protein but absent in others. We reasoned that the labile nature of these disulfides signifies a propensity for cleavage and so possible allosteric regulation of the protein in which the bond resides. A total of 511 labile disulfide bonds were identified. The labile disulfides are more stressed than the average bond, being characterized by high average torsional strain and stretching of the sulfur–sulfur bond and neighbouring bond angles. This pre-stress likely underpins their susceptibility to cleavage. The coagulation, complement and oxygen-sensing hypoxia inducible factor-1 pathways, which are known or have been suggested to be regulated by allosteric disulfides, are enriched in proteins containing labile disulfides. The identification of labile disulfide bonds will facilitate the study of this post-translational modification. |
format | Online Article Text |
id | pubmed-5830721 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-58307212018-03-07 Identification of allosteric disulfides from labile bonds in X-ray structures Pijning, Aster E. Chiu, Joyce Yeo, Reichelle X. Wong, Jason W. H. Hogg, Philip J. R Soc Open Sci Biochemistry and Biophysics Protein disulfide bonds link pairs of cysteine sulfur atoms and are either structural or functional motifs. The allosteric disulfides control the function of the protein in which they reside when cleaved or formed. Here, we identify potential allosteric disulfides in all Protein Data Bank X-ray structures from bonds that are present in some molecules of a protein crystal but absent in others, or present in some structures of a protein but absent in others. We reasoned that the labile nature of these disulfides signifies a propensity for cleavage and so possible allosteric regulation of the protein in which the bond resides. A total of 511 labile disulfide bonds were identified. The labile disulfides are more stressed than the average bond, being characterized by high average torsional strain and stretching of the sulfur–sulfur bond and neighbouring bond angles. This pre-stress likely underpins their susceptibility to cleavage. The coagulation, complement and oxygen-sensing hypoxia inducible factor-1 pathways, which are known or have been suggested to be regulated by allosteric disulfides, are enriched in proteins containing labile disulfides. The identification of labile disulfide bonds will facilitate the study of this post-translational modification. The Royal Society Publishing 2018-02-07 /pmc/articles/PMC5830721/ /pubmed/29515832 http://dx.doi.org/10.1098/rsos.171058 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Biochemistry and Biophysics Pijning, Aster E. Chiu, Joyce Yeo, Reichelle X. Wong, Jason W. H. Hogg, Philip J. Identification of allosteric disulfides from labile bonds in X-ray structures |
title | Identification of allosteric disulfides from labile bonds in X-ray structures |
title_full | Identification of allosteric disulfides from labile bonds in X-ray structures |
title_fullStr | Identification of allosteric disulfides from labile bonds in X-ray structures |
title_full_unstemmed | Identification of allosteric disulfides from labile bonds in X-ray structures |
title_short | Identification of allosteric disulfides from labile bonds in X-ray structures |
title_sort | identification of allosteric disulfides from labile bonds in x-ray structures |
topic | Biochemistry and Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830721/ https://www.ncbi.nlm.nih.gov/pubmed/29515832 http://dx.doi.org/10.1098/rsos.171058 |
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