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Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity

[Image: see text] Non-enzymatic posttranslational modifications are believed to affect at least 30% of human proteins, commonly termed glycation. Many of these modifications are implicated in various pathological conditions, e.g., cataract, diabetes, neurodegenerative diseases, and cancer. Chemical...

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Autores principales: Mukherjee, Somnath, Vogl, Dominik P., Becker, Christian F. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442856/
https://www.ncbi.nlm.nih.gov/pubmed/37449780
http://dx.doi.org/10.1021/acschembio.3c00214
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author Mukherjee, Somnath
Vogl, Dominik P.
Becker, Christian F. W.
author_facet Mukherjee, Somnath
Vogl, Dominik P.
Becker, Christian F. W.
author_sort Mukherjee, Somnath
collection PubMed
description [Image: see text] Non-enzymatic posttranslational modifications are believed to affect at least 30% of human proteins, commonly termed glycation. Many of these modifications are implicated in various pathological conditions, e.g., cataract, diabetes, neurodegenerative diseases, and cancer. Chemical protein synthesis enables access to full-length proteins carrying site-specific modifications. One such modification, argpyrimidine (Apy), has been detected in human small heat shock protein Hsp27 and closely related proteins in patient-derived tissues. Thus far, studies have looked into only artificial mixtures of Apy modifications, and only one has analyzed Apy188. We were interested in understanding the impact of such individual Apy modifications on five different arginine sites within the crucial N-terminal domain of Hsp27. By combining protein semisynthesis with biochemical assays on semisynthetic Hsp27 analogues with single-point Apy modification at those sites, we have shown how a seemingly minimal modification within this region results in dramatically altered functional attributes.
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spelling pubmed-104428562023-08-23 Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity Mukherjee, Somnath Vogl, Dominik P. Becker, Christian F. W. ACS Chem Biol [Image: see text] Non-enzymatic posttranslational modifications are believed to affect at least 30% of human proteins, commonly termed glycation. Many of these modifications are implicated in various pathological conditions, e.g., cataract, diabetes, neurodegenerative diseases, and cancer. Chemical protein synthesis enables access to full-length proteins carrying site-specific modifications. One such modification, argpyrimidine (Apy), has been detected in human small heat shock protein Hsp27 and closely related proteins in patient-derived tissues. Thus far, studies have looked into only artificial mixtures of Apy modifications, and only one has analyzed Apy188. We were interested in understanding the impact of such individual Apy modifications on five different arginine sites within the crucial N-terminal domain of Hsp27. By combining protein semisynthesis with biochemical assays on semisynthetic Hsp27 analogues with single-point Apy modification at those sites, we have shown how a seemingly minimal modification within this region results in dramatically altered functional attributes. American Chemical Society 2023-07-14 /pmc/articles/PMC10442856/ /pubmed/37449780 http://dx.doi.org/10.1021/acschembio.3c00214 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Mukherjee, Somnath
Vogl, Dominik P.
Becker, Christian F. W.
Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity
title Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity
title_full Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity
title_fullStr Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity
title_full_unstemmed Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity
title_short Site-Specific Glycation of Human Heat Shock Protein (Hsp27) Enhances Its Chaperone Activity
title_sort site-specific glycation of human heat shock protein (hsp27) enhances its chaperone activity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442856/
https://www.ncbi.nlm.nih.gov/pubmed/37449780
http://dx.doi.org/10.1021/acschembio.3c00214
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