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Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase
Uracil-DNA glycosylases (UDGs) are highly conserved proteins that can be found in a wide range of organisms, and are involved in the DNA repair and host defense systems. UDG activity is controlled by various cellular factors, including the uracil-DNA glycosylase inhibitors, which are DNA mimic prote...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872100/ https://www.ncbi.nlm.nih.gov/pubmed/26980279 http://dx.doi.org/10.1093/nar/gkw185 |
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author | Wang, Hao-Ching Ho, Chun-Han Chou, Chia-Cheng Ko, Tzu-Ping Huang, Ming-Fen Hsu, Kai-Cheng Wang, Andrew H.-J. |
author_facet | Wang, Hao-Ching Ho, Chun-Han Chou, Chia-Cheng Ko, Tzu-Ping Huang, Ming-Fen Hsu, Kai-Cheng Wang, Andrew H.-J. |
author_sort | Wang, Hao-Ching |
collection | PubMed |
description | Uracil-DNA glycosylases (UDGs) are highly conserved proteins that can be found in a wide range of organisms, and are involved in the DNA repair and host defense systems. UDG activity is controlled by various cellular factors, including the uracil-DNA glycosylase inhibitors, which are DNA mimic proteins that prevent the DNA binding sites of UDGs from interacting with their DNA substrate. To date, only three uracil-DNA glycosylase inhibitors, phage UGI, p56, and Staphylococcus aureus SAUGI, have been determined. We show here that SAUGI has differential inhibitory effects on UDGs from human, bacteria, Herpes simplex virus (HSV; human herpesvirus 1) and Epstein-Barr virus (EBV; human herpesvirus 4). Newly determined crystal structures of SAUGI/human UDG and a SAUGI/HSVUDG complex were used to explain the differential binding activities of SAUGI on these two UDGs. Structural-based protein engineering was further used to modulate the inhibitory ability of SAUGI on human UDG and HSVUDG. The results of this work extend our understanding of DNA mimics as well as potentially opening the way for novel therapeutic applications for this kind of protein. |
format | Online Article Text |
id | pubmed-4872100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48721002016-05-27 Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase Wang, Hao-Ching Ho, Chun-Han Chou, Chia-Cheng Ko, Tzu-Ping Huang, Ming-Fen Hsu, Kai-Cheng Wang, Andrew H.-J. Nucleic Acids Res Structural Biology Uracil-DNA glycosylases (UDGs) are highly conserved proteins that can be found in a wide range of organisms, and are involved in the DNA repair and host defense systems. UDG activity is controlled by various cellular factors, including the uracil-DNA glycosylase inhibitors, which are DNA mimic proteins that prevent the DNA binding sites of UDGs from interacting with their DNA substrate. To date, only three uracil-DNA glycosylase inhibitors, phage UGI, p56, and Staphylococcus aureus SAUGI, have been determined. We show here that SAUGI has differential inhibitory effects on UDGs from human, bacteria, Herpes simplex virus (HSV; human herpesvirus 1) and Epstein-Barr virus (EBV; human herpesvirus 4). Newly determined crystal structures of SAUGI/human UDG and a SAUGI/HSVUDG complex were used to explain the differential binding activities of SAUGI on these two UDGs. Structural-based protein engineering was further used to modulate the inhibitory ability of SAUGI on human UDG and HSVUDG. The results of this work extend our understanding of DNA mimics as well as potentially opening the way for novel therapeutic applications for this kind of protein. Oxford University Press 2016-05-19 2016-03-14 /pmc/articles/PMC4872100/ /pubmed/26980279 http://dx.doi.org/10.1093/nar/gkw185 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Structural Biology Wang, Hao-Ching Ho, Chun-Han Chou, Chia-Cheng Ko, Tzu-Ping Huang, Ming-Fen Hsu, Kai-Cheng Wang, Andrew H.-J. Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase |
title | Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase |
title_full | Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase |
title_fullStr | Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase |
title_full_unstemmed | Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase |
title_short | Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase |
title_sort | using structural-based protein engineering to modulate the differential inhibition effects of saugi on human and hsv uracil dna glycosylase |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872100/ https://www.ncbi.nlm.nih.gov/pubmed/26980279 http://dx.doi.org/10.1093/nar/gkw185 |
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