Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth
Phosphoglycerate mutase 1 (PGAM1) catalyzes the eighth step of glycolysis and is often found upregulated in cancer cells. To test the hypothesis that the phosphorylation of tyrosine 26 residue of PGAM1 greatly enhances its activity, we performed both conventional and steered molecular dynamics simul...
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| Veröffentlicht in: | Oncotarget 2017-02, Vol.8 (7), p.12093-12107 |
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| creator | Wang, Yan Cai, Wen-Sheng Chen, Luonan Wang, Guanyu |
| description | Phosphoglycerate mutase 1 (PGAM1) catalyzes the eighth step of glycolysis and is often found upregulated in cancer cells. To test the hypothesis that the phosphorylation of tyrosine 26 residue of PGAM1 greatly enhances its activity, we performed both conventional and steered molecular dynamics simulations on the binding and unbinding of PGAM1 to its substrates, with tyrosine 26 either phosphorylated or not. We analyzed the simulated data in terms of structural stability, hydrogen bond formation, binding free energy, etc. We found that tyrosine 26 phosphorylation enhances the binding of PGAM1 to its substrates through generating electrostatic environment and structural features that are advantageous to the binding. Our results may provide valuable insights into computer-aided design of drugs that specifically target cancer cells with PGAM1 tyrosine 26 phosphorylated. |
| doi_str_mv | 10.18632/oncotarget.14517 |
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To test the hypothesis that the phosphorylation of tyrosine 26 residue of PGAM1 greatly enhances its activity, we performed both conventional and steered molecular dynamics simulations on the binding and unbinding of PGAM1 to its substrates, with tyrosine 26 either phosphorylated or not. We analyzed the simulated data in terms of structural stability, hydrogen bond formation, binding free energy, etc. We found that tyrosine 26 phosphorylation enhances the binding of PGAM1 to its substrates through generating electrostatic environment and structural features that are advantageous to the binding. Our results may provide valuable insights into computer-aided design of drugs that specifically target cancer cells with PGAM1 tyrosine 26 phosphorylated.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.14517</identifier><identifier>PMID: 28076845</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>2,3-Diphosphoglycerate - chemistry ; 2,3-Diphosphoglycerate - metabolism ; Algorithms ; Amino Acid Sequence ; Glyceric Acids - chemistry ; Glyceric Acids - metabolism ; Glycolysis ; Humans ; Hydrogen Bonding ; Molecular Dynamics Simulation ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; Phosphoglycerate Mutase - chemistry ; Phosphoglycerate Mutase - genetics ; Phosphoglycerate Mutase - metabolism ; Phosphorylation ; Principal Component Analysis ; Protein Binding ; Research Paper ; Sequence Homology, Amino Acid ; Static Electricity ; Substrate Specificity ; Thermodynamics ; Tyrosine - chemistry ; Tyrosine - genetics ; Tyrosine - metabolism</subject><ispartof>Oncotarget, 2017-02, Vol.8 (7), p.12093-12107</ispartof><rights>Copyright: © 2017 Wang et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-c421364af06cafb0bfaf30dcd552cb46568e243321a383526456984f3d3554443</citedby><cites>FETCH-LOGICAL-c422t-c421364af06cafb0bfaf30dcd552cb46568e243321a383526456984f3d3554443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355328/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355328/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28076845$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Cai, Wen-Sheng</creatorcontrib><creatorcontrib>Chen, Luonan</creatorcontrib><creatorcontrib>Wang, Guanyu</creatorcontrib><title>Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Phosphoglycerate mutase 1 (PGAM1) catalyzes the eighth step of glycolysis and is often found upregulated in cancer cells. To test the hypothesis that the phosphorylation of tyrosine 26 residue of PGAM1 greatly enhances its activity, we performed both conventional and steered molecular dynamics simulations on the binding and unbinding of PGAM1 to its substrates, with tyrosine 26 either phosphorylated or not. We analyzed the simulated data in terms of structural stability, hydrogen bond formation, binding free energy, etc. We found that tyrosine 26 phosphorylation enhances the binding of PGAM1 to its substrates through generating electrostatic environment and structural features that are advantageous to the binding. Our results may provide valuable insights into computer-aided design of drugs that specifically target cancer cells with PGAM1 tyrosine 26 phosphorylated.</description><subject>2,3-Diphosphoglycerate - chemistry</subject><subject>2,3-Diphosphoglycerate - metabolism</subject><subject>Algorithms</subject><subject>Amino Acid Sequence</subject><subject>Glyceric Acids - chemistry</subject><subject>Glyceric Acids - metabolism</subject><subject>Glycolysis</subject><subject>Humans</subject><subject>Hydrogen Bonding</subject><subject>Molecular Dynamics Simulation</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Phosphoglycerate Mutase - chemistry</subject><subject>Phosphoglycerate Mutase - genetics</subject><subject>Phosphoglycerate Mutase - metabolism</subject><subject>Phosphorylation</subject><subject>Principal Component Analysis</subject><subject>Protein Binding</subject><subject>Research Paper</subject><subject>Sequence Homology, Amino Acid</subject><subject>Static Electricity</subject><subject>Substrate Specificity</subject><subject>Thermodynamics</subject><subject>Tyrosine - chemistry</subject><subject>Tyrosine - genetics</subject><subject>Tyrosine - metabolism</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1P3DAQtaoiFgE_gEvlYy8L8ed6L5WqVQtIVL3A2fI6k6yrJJPaDih_hN_bBLbbraXxx7w3b0Z-hFyx4poZLfgNdh6zizXkayYVW30gZ2wt10uulPh4dF-Qy5R-FdNScmX4-pQsuClW2kh1Rl5_YAN-aFyk5di5NvhEU2inRA7Y0QjP4JpEd_hC-x2mKeK4x7CieYyYQgeU6_m5Z9TN6CG6DLQdsktAGR36CPUsConOMDZjCom6rqR9xBbnfB5ajLSO-JJ3F-SkmvrC5f48J0_fvz1u7pYPP2_vN18fll5ynuedCS1dVWjvqm2xrVwlitKXSnG_lVppA1wKwZkTRiiupdJrIytRCqWklOKcfHnX7YdtC6WHLkfX2D6G1sXRogv2f6QLO1vjs1WTgOBmEvi8F4j4e4CUbRuSh6ZxHeCQLDPKsMKs1Exl71Q_fVqKUB3asMK-WWr_WWrfLJ1qPh3Pd6j4a6D4A_ZKpTc</recordid><startdate>20170214</startdate><enddate>20170214</enddate><creator>Wang, Yan</creator><creator>Cai, Wen-Sheng</creator><creator>Chen, Luonan</creator><creator>Wang, Guanyu</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170214</creationdate><title>Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth</title><author>Wang, Yan ; Cai, Wen-Sheng ; Chen, Luonan ; Wang, Guanyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-c421364af06cafb0bfaf30dcd552cb46568e243321a383526456984f3d3554443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>2,3-Diphosphoglycerate - chemistry</topic><topic>2,3-Diphosphoglycerate - metabolism</topic><topic>Algorithms</topic><topic>Amino Acid Sequence</topic><topic>Glyceric Acids - chemistry</topic><topic>Glyceric Acids - metabolism</topic><topic>Glycolysis</topic><topic>Humans</topic><topic>Hydrogen Bonding</topic><topic>Molecular Dynamics Simulation</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Phosphoglycerate Mutase - chemistry</topic><topic>Phosphoglycerate Mutase - genetics</topic><topic>Phosphoglycerate Mutase - metabolism</topic><topic>Phosphorylation</topic><topic>Principal Component Analysis</topic><topic>Protein Binding</topic><topic>Research Paper</topic><topic>Sequence Homology, Amino Acid</topic><topic>Static Electricity</topic><topic>Substrate Specificity</topic><topic>Thermodynamics</topic><topic>Tyrosine - chemistry</topic><topic>Tyrosine - genetics</topic><topic>Tyrosine - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Cai, Wen-Sheng</creatorcontrib><creatorcontrib>Chen, Luonan</creatorcontrib><creatorcontrib>Wang, Guanyu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yan</au><au>Cai, Wen-Sheng</au><au>Chen, Luonan</au><au>Wang, Guanyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-02-14</date><risdate>2017</risdate><volume>8</volume><issue>7</issue><spage>12093</spage><epage>12107</epage><pages>12093-12107</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Phosphoglycerate mutase 1 (PGAM1) catalyzes the eighth step of glycolysis and is often found upregulated in cancer cells. To test the hypothesis that the phosphorylation of tyrosine 26 residue of PGAM1 greatly enhances its activity, we performed both conventional and steered molecular dynamics simulations on the binding and unbinding of PGAM1 to its substrates, with tyrosine 26 either phosphorylated or not. We analyzed the simulated data in terms of structural stability, hydrogen bond formation, binding free energy, etc. We found that tyrosine 26 phosphorylation enhances the binding of PGAM1 to its substrates through generating electrostatic environment and structural features that are advantageous to the binding. Our results may provide valuable insights into computer-aided design of drugs that specifically target cancer cells with PGAM1 tyrosine 26 phosphorylated.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28076845</pmid><doi>10.18632/oncotarget.14517</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 2,3-Diphosphoglycerate - chemistry 2,3-Diphosphoglycerate - metabolism Algorithms Amino Acid Sequence Glyceric Acids - chemistry Glyceric Acids - metabolism Glycolysis Humans Hydrogen Bonding Molecular Dynamics Simulation Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Phosphoglycerate Mutase - chemistry Phosphoglycerate Mutase - genetics Phosphoglycerate Mutase - metabolism Phosphorylation Principal Component Analysis Protein Binding Research Paper Sequence Homology, Amino Acid Static Electricity Substrate Specificity Thermodynamics Tyrosine - chemistry Tyrosine - genetics Tyrosine - metabolism |
| title | Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth |
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