Molecular mechanism of green tea polyphenol epicatechin gallate attenuating Staphylococcus aureus pathogenicity by targeting Ser/Thr phosphatase Stp1
In this study, through virtual screening and bioactivity assays, we discovered that (-)-epicatechin gallate (ECG), a polyphenol compound extracted from green tea, demonstrated marked anti-Ser/Thr phosphatase (Stp1) activity towards ( ) with an IC value of 8.35 μM. By targeting Stp1, ECG prevented th...
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| Veröffentlicht in: | Food & function 2023-05, Vol.14 (10), p.4792-4806 |
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| creator | Gao, Yawen Wang, Hongsu Li, Xuening Niu, Xiaodi |
| description | In this study, through virtual screening and
bioactivity assays, we discovered that (-)-epicatechin gallate (ECG), a polyphenol compound extracted from green tea, demonstrated marked anti-Ser/Thr phosphatase (Stp1) activity towards
(
) with an IC
value of 8.35 μM. By targeting
Stp1, ECG prevented the up-regulation of virulence gene and the formation of antibody membrane and protected the mice from
infection. Through MD simulation, the allosteric inhibitory mechanism of ECG on Stp1 was determined. The Stp1-ECG complex model underwent a significant change in conformation; its flap subdomain changed from opening to closing, whereas Stp1 activity was lost when bound to ECG. In addition, the MD simulation results of Stp1 and several tea polyphenol compounds showed that gallate groups and fewer adjacent phenolic hydroxyl groups contributed to the binding of Stp1 and inhibitors. As an inhibitor targeting
Stp1, ECG reduced the pathogenicity of
without inhibiting
, which largely reduced the possibility of drug resistance. Our findings demonstrated a novel molecular mechanism of green tea as the usual drink against
infection and elucidated the future design of allosteric inhibitors targeting Stp1. |
| doi_str_mv | 10.1039/d3fo00170a |
| format | Article |
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bioactivity assays, we discovered that (-)-epicatechin gallate (ECG), a polyphenol compound extracted from green tea, demonstrated marked anti-Ser/Thr phosphatase (Stp1) activity towards
(
) with an IC
value of 8.35 μM. By targeting
Stp1, ECG prevented the up-regulation of virulence gene and the formation of antibody membrane and protected the mice from
infection. Through MD simulation, the allosteric inhibitory mechanism of ECG on Stp1 was determined. The Stp1-ECG complex model underwent a significant change in conformation; its flap subdomain changed from opening to closing, whereas Stp1 activity was lost when bound to ECG. In addition, the MD simulation results of Stp1 and several tea polyphenol compounds showed that gallate groups and fewer adjacent phenolic hydroxyl groups contributed to the binding of Stp1 and inhibitors. As an inhibitor targeting
Stp1, ECG reduced the pathogenicity of
without inhibiting
, which largely reduced the possibility of drug resistance. Our findings demonstrated a novel molecular mechanism of green tea as the usual drink against
infection and elucidated the future design of allosteric inhibitors targeting Stp1.</description><identifier>ISSN: 2042-6496</identifier><identifier>EISSN: 2042-650X</identifier><identifier>DOI: 10.1039/d3fo00170a</identifier><identifier>PMID: 37128867</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Allosteric properties ; Animals ; Antibodies ; Biological activity ; Catechin - chemistry ; Catechin - pharmacology ; Cocoa ; Conformation ; Drug resistance ; Epicatechin ; Green tea ; Hydroxyl groups ; Inhibitors ; Mice ; Molecular modelling ; Pathogenicity ; Pathogens ; Phenolic compounds ; Phenols ; Phosphatase ; Phosphoric Monoester Hydrolases ; Polyphenols - pharmacology ; Simulation ; Staphylococcal Infections - drug therapy ; Staphylococcus aureus ; Tea ; Tea - chemistry ; Virulence</subject><ispartof>Food & function, 2023-05, Vol.14 (10), p.4792-4806</ispartof><rights>Copyright Royal Society of Chemistry 2023</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c274t-5d2ac50ee70f918e54b6f3c4044353756c54e502af67ef4c02cdeb6fbea6ef633</cites><orcidid>0000-0001-6640-0427</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37128867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Yawen</creatorcontrib><creatorcontrib>Wang, Hongsu</creatorcontrib><creatorcontrib>Li, Xuening</creatorcontrib><creatorcontrib>Niu, Xiaodi</creatorcontrib><title>Molecular mechanism of green tea polyphenol epicatechin gallate attenuating Staphylococcus aureus pathogenicity by targeting Ser/Thr phosphatase Stp1</title><title>Food & function</title><addtitle>Food Funct</addtitle><description>In this study, through virtual screening and
bioactivity assays, we discovered that (-)-epicatechin gallate (ECG), a polyphenol compound extracted from green tea, demonstrated marked anti-Ser/Thr phosphatase (Stp1) activity towards
(
) with an IC
value of 8.35 μM. By targeting
Stp1, ECG prevented the up-regulation of virulence gene and the formation of antibody membrane and protected the mice from
infection. Through MD simulation, the allosteric inhibitory mechanism of ECG on Stp1 was determined. The Stp1-ECG complex model underwent a significant change in conformation; its flap subdomain changed from opening to closing, whereas Stp1 activity was lost when bound to ECG. In addition, the MD simulation results of Stp1 and several tea polyphenol compounds showed that gallate groups and fewer adjacent phenolic hydroxyl groups contributed to the binding of Stp1 and inhibitors. As an inhibitor targeting
Stp1, ECG reduced the pathogenicity of
without inhibiting
, which largely reduced the possibility of drug resistance. Our findings demonstrated a novel molecular mechanism of green tea as the usual drink against
infection and elucidated the future design of allosteric inhibitors targeting Stp1.</description><subject>Allosteric properties</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biological activity</subject><subject>Catechin - chemistry</subject><subject>Catechin - pharmacology</subject><subject>Cocoa</subject><subject>Conformation</subject><subject>Drug resistance</subject><subject>Epicatechin</subject><subject>Green tea</subject><subject>Hydroxyl groups</subject><subject>Inhibitors</subject><subject>Mice</subject><subject>Molecular modelling</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Phenolic compounds</subject><subject>Phenols</subject><subject>Phosphatase</subject><subject>Phosphoric Monoester Hydrolases</subject><subject>Polyphenols - pharmacology</subject><subject>Simulation</subject><subject>Staphylococcal Infections - drug therapy</subject><subject>Staphylococcus aureus</subject><subject>Tea</subject><subject>Tea - chemistry</subject><subject>Virulence</subject><issn>2042-6496</issn><issn>2042-650X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0b9u1TAUBvAIgWhVuvAAyBILQrrUjv9mrAoFpKIOFIktOtf3OEmV2MZ2hjwI74vLbRnwcs7w8ydbX9O8ZvQDo7y7OHAXKGWawrPmtKWi3SlJfz5_2kWnTprznO9pPbzrTGdeNidcs9YYpU-b39_CjHadIZEF7Qh-ygsJjgwJ0ZOCQGKYtziiDzPBOFkolU2eDDDPdSdQCvoVyuQH8r1AHLc52GDtmgmsCeuIUMYwoJ_sVDay30iBNODxAqaLuzGROIYcRyiQsYZE9qp54WDOeP44z5of15_urr7sbm4_f726vNnZVouyk4cWrKSImrqOGZRirxy3ggrBJddSWSlQ0hac0uiEpa09YCV7BIVOcX7WvDvmxhR-rZhLv0zZYv2Zx7DmvjXUSKMpU5W-_Y_ehzX5-rqqmNKGMvOg3h-VTSHnhK6PaVogbT2j_UNf_Ud-ffu3r8uK3zxGrvsFD__oUzv8Dz3-k7M</recordid><startdate>20230522</startdate><enddate>20230522</enddate><creator>Gao, Yawen</creator><creator>Wang, Hongsu</creator><creator>Li, Xuening</creator><creator>Niu, Xiaodi</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6640-0427</orcidid></search><sort><creationdate>20230522</creationdate><title>Molecular mechanism of green tea polyphenol epicatechin gallate attenuating Staphylococcus aureus pathogenicity by targeting Ser/Thr phosphatase Stp1</title><author>Gao, Yawen ; Wang, Hongsu ; Li, Xuening ; Niu, Xiaodi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c274t-5d2ac50ee70f918e54b6f3c4044353756c54e502af67ef4c02cdeb6fbea6ef633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Allosteric properties</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biological activity</topic><topic>Catechin - chemistry</topic><topic>Catechin - pharmacology</topic><topic>Cocoa</topic><topic>Conformation</topic><topic>Drug resistance</topic><topic>Epicatechin</topic><topic>Green tea</topic><topic>Hydroxyl groups</topic><topic>Inhibitors</topic><topic>Mice</topic><topic>Molecular modelling</topic><topic>Pathogenicity</topic><topic>Pathogens</topic><topic>Phenolic compounds</topic><topic>Phenols</topic><topic>Phosphatase</topic><topic>Phosphoric Monoester Hydrolases</topic><topic>Polyphenols - pharmacology</topic><topic>Simulation</topic><topic>Staphylococcal Infections - drug therapy</topic><topic>Staphylococcus aureus</topic><topic>Tea</topic><topic>Tea - chemistry</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gao, Yawen</creatorcontrib><creatorcontrib>Wang, Hongsu</creatorcontrib><creatorcontrib>Li, Xuening</creatorcontrib><creatorcontrib>Niu, Xiaodi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Food & function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gao, Yawen</au><au>Wang, Hongsu</au><au>Li, Xuening</au><au>Niu, Xiaodi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular mechanism of green tea polyphenol epicatechin gallate attenuating Staphylococcus aureus pathogenicity by targeting Ser/Thr phosphatase Stp1</atitle><jtitle>Food & function</jtitle><addtitle>Food Funct</addtitle><date>2023-05-22</date><risdate>2023</risdate><volume>14</volume><issue>10</issue><spage>4792</spage><epage>4806</epage><pages>4792-4806</pages><issn>2042-6496</issn><eissn>2042-650X</eissn><abstract>In this study, through virtual screening and
bioactivity assays, we discovered that (-)-epicatechin gallate (ECG), a polyphenol compound extracted from green tea, demonstrated marked anti-Ser/Thr phosphatase (Stp1) activity towards
(
) with an IC
value of 8.35 μM. By targeting
Stp1, ECG prevented the up-regulation of virulence gene and the formation of antibody membrane and protected the mice from
infection. Through MD simulation, the allosteric inhibitory mechanism of ECG on Stp1 was determined. The Stp1-ECG complex model underwent a significant change in conformation; its flap subdomain changed from opening to closing, whereas Stp1 activity was lost when bound to ECG. In addition, the MD simulation results of Stp1 and several tea polyphenol compounds showed that gallate groups and fewer adjacent phenolic hydroxyl groups contributed to the binding of Stp1 and inhibitors. As an inhibitor targeting
Stp1, ECG reduced the pathogenicity of
without inhibiting
, which largely reduced the possibility of drug resistance. Our findings demonstrated a novel molecular mechanism of green tea as the usual drink against
infection and elucidated the future design of allosteric inhibitors targeting Stp1.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>37128867</pmid><doi>10.1039/d3fo00170a</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-6640-0427</orcidid></addata></record> |
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| subjects | Allosteric properties Animals Antibodies Biological activity Catechin - chemistry Catechin - pharmacology Cocoa Conformation Drug resistance Epicatechin Green tea Hydroxyl groups Inhibitors Mice Molecular modelling Pathogenicity Pathogens Phenolic compounds Phenols Phosphatase Phosphoric Monoester Hydrolases Polyphenols - pharmacology Simulation Staphylococcal Infections - drug therapy Staphylococcus aureus Tea Tea - chemistry Virulence |
| title | Molecular mechanism of green tea polyphenol epicatechin gallate attenuating Staphylococcus aureus pathogenicity by targeting Ser/Thr phosphatase Stp1 |
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