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Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion
Pathogenic bacteria produce a wide variety of virulence factors that are considered to be potential antibiotic targets. In this study, we report the crystal structure of a novel S. pneumoniae virulence factor, GHIP, which is a streptococcus-specific glycosyl hydrolase. This novel structure exhibits...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712932/ https://www.ncbi.nlm.nih.gov/pubmed/23874703 http://dx.doi.org/10.1371/journal.pone.0068647 |
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author | Niu, Siqiang Luo, Miao Tang, Jian Zhou, Hua Zhang, Yangli Min, Xun Cai, Xuefei Zhang, Wenlu Xu, Wenchu Li, Defeng Ding, Jingjin Hu, Yonglin Wang, Dacheng Huang, Ailong Yin, Yibin Wang, Deqiang |
author_facet | Niu, Siqiang Luo, Miao Tang, Jian Zhou, Hua Zhang, Yangli Min, Xun Cai, Xuefei Zhang, Wenlu Xu, Wenchu Li, Defeng Ding, Jingjin Hu, Yonglin Wang, Dacheng Huang, Ailong Yin, Yibin Wang, Deqiang |
author_sort | Niu, Siqiang |
collection | PubMed |
description | Pathogenic bacteria produce a wide variety of virulence factors that are considered to be potential antibiotic targets. In this study, we report the crystal structure of a novel S. pneumoniae virulence factor, GHIP, which is a streptococcus-specific glycosyl hydrolase. This novel structure exhibits an α/β-barrel fold that slightly differs from other characterized hydrolases. The GHIP active site, located at the negatively charged groove in the barrel, is very similar to the active site in known peptidoglycan hydrolases. Functionally, GHIP exhibited weak enzymatic activity to hydrolyze the PNP-(GlcNAc)(5) peptidoglycan by the general acid/base catalytic mechanism. Animal experiments demonstrated a marked attenuation of S. pneumoniae-mediated virulence in mice infected by ΔGHIP-deficient strains, suggesting that GHIP functions as a novel S. pneumoniae virulence factor. Furthermore, GHIP participates in allowing S. pneumoniae to colonize the nasopharynx and invade host epithelial cells. Taken together, these findings suggest that GHIP can potentially serve as an antibiotic target to effectively treat streptococcus-mediated infection. |
format | Online Article Text |
id | pubmed-3712932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37129322013-07-19 Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion Niu, Siqiang Luo, Miao Tang, Jian Zhou, Hua Zhang, Yangli Min, Xun Cai, Xuefei Zhang, Wenlu Xu, Wenchu Li, Defeng Ding, Jingjin Hu, Yonglin Wang, Dacheng Huang, Ailong Yin, Yibin Wang, Deqiang PLoS One Research Article Pathogenic bacteria produce a wide variety of virulence factors that are considered to be potential antibiotic targets. In this study, we report the crystal structure of a novel S. pneumoniae virulence factor, GHIP, which is a streptococcus-specific glycosyl hydrolase. This novel structure exhibits an α/β-barrel fold that slightly differs from other characterized hydrolases. The GHIP active site, located at the negatively charged groove in the barrel, is very similar to the active site in known peptidoglycan hydrolases. Functionally, GHIP exhibited weak enzymatic activity to hydrolyze the PNP-(GlcNAc)(5) peptidoglycan by the general acid/base catalytic mechanism. Animal experiments demonstrated a marked attenuation of S. pneumoniae-mediated virulence in mice infected by ΔGHIP-deficient strains, suggesting that GHIP functions as a novel S. pneumoniae virulence factor. Furthermore, GHIP participates in allowing S. pneumoniae to colonize the nasopharynx and invade host epithelial cells. Taken together, these findings suggest that GHIP can potentially serve as an antibiotic target to effectively treat streptococcus-mediated infection. Public Library of Science 2013-07-16 /pmc/articles/PMC3712932/ /pubmed/23874703 http://dx.doi.org/10.1371/journal.pone.0068647 Text en © 2013 Niu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Niu, Siqiang Luo, Miao Tang, Jian Zhou, Hua Zhang, Yangli Min, Xun Cai, Xuefei Zhang, Wenlu Xu, Wenchu Li, Defeng Ding, Jingjin Hu, Yonglin Wang, Dacheng Huang, Ailong Yin, Yibin Wang, Deqiang Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion |
title | Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion |
title_full | Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion |
title_fullStr | Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion |
title_full_unstemmed | Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion |
title_short | Structural Basis of the Novel S. pneumoniae Virulence Factor, GHIP, a Glycosyl Hydrolase 25 Participating in Host-Cell Invasion |
title_sort | structural basis of the novel s. pneumoniae virulence factor, ghip, a glycosyl hydrolase 25 participating in host-cell invasion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712932/ https://www.ncbi.nlm.nih.gov/pubmed/23874703 http://dx.doi.org/10.1371/journal.pone.0068647 |
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