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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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.
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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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