mTOR kinase structure, mechanism and regulation
The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13...
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Veröffentlicht in: | Nature (London) 2013-05, Vol.497 (7448), p.217-223 |
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description | The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12–rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access.
In vitro
biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin–FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.
Structure of mTOR kinase
The mTOR (mammalian target of rapamycin) pathway is a central regulator of cell growth in response to environmental signals such as energy, nutrients and growth factors, and is misregulated in cancer and metabolic diseases. Here the first crystal structures of the mTOR kinase are presented. The 3.2 Å crystal structures of the enzyme bound to a positive regulator and to small-molecule ATP-competitive inhibitors reveal an intrinsically active kinase, and explain how the rapamycin–FKBP12 complex blocks recruitment of substrates to the kinase domain. |
doi_str_mv | 10.1038/nature12122 |
format | Article |
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In vitro
biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin–FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.
Structure of mTOR kinase
The mTOR (mammalian target of rapamycin) pathway is a central regulator of cell growth in response to environmental signals such as energy, nutrients and growth factors, and is misregulated in cancer and metabolic diseases. Here the first crystal structures of the mTOR kinase are presented. The 3.2 Å crystal structures of the enzyme bound to a positive regulator and to small-molecule ATP-competitive inhibitors reveal an intrinsically active kinase, and explain how the rapamycin–FKBP12 complex blocks recruitment of substrates to the kinase domain.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature12122</identifier><identifier>PMID: 23636326</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/45/275 ; 631/535/1266 ; 631/80/83/2359 ; 631/80/86/2368 ; Adaptor Proteins, Signal Transducing - chemistry ; Adaptor Proteins, Signal Transducing - metabolism ; Adenosine Triphosphate - chemistry ; Adenosine Triphosphate - metabolism ; ATP ; Catalytic Domain - drug effects ; Crystal structure ; Crystallography, X-Ray ; Enzymes ; Furans - chemistry ; Furans - pharmacology ; Growth factors ; Humanities and Social Sciences ; Humans ; Indoles - chemistry ; Indoles - metabolism ; Indoles - pharmacology ; Kinases ; Magnesium - chemistry ; Magnesium - metabolism ; Mammals ; Models, Molecular ; mTOR Associated Protein, LST8 Homolog ; multidisciplinary ; Naphthyridines - chemistry ; Naphthyridines - metabolism ; Naphthyridines - pharmacology ; Protein Structure, Tertiary - drug effects ; Proteins ; Purines - chemistry ; Purines - metabolism ; Purines - pharmacology ; Pyridines - chemistry ; Pyridines - pharmacology ; Pyrimidines - chemistry ; Pyrimidines - pharmacology ; Ribosomal Protein S6 Kinases, 70-kDa - metabolism ; Science ; Sirolimus - chemistry ; Sirolimus - metabolism ; Sirolimus - pharmacology ; Structure-Activity Relationship ; Tacrolimus Binding Protein 1A - chemistry ; Tacrolimus Binding Protein 1A - metabolism ; Tacrolimus Binding Protein 1A - pharmacology ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; TOR Serine-Threonine Kinases - chemistry ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Nature (London), 2013-05, Vol.497 (7448), p.217-223</ispartof><rights>Springer Nature Limited 2013</rights><rights>Copyright Nature Publishing Group May 9, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-55d267799a9bc4f9c9406fd20ca16bb525a17c5f2486ffe5b9e0e762c169918f3</citedby><cites>FETCH-LOGICAL-c391t-55d267799a9bc4f9c9406fd20ca16bb525a17c5f2486ffe5b9e0e762c169918f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23636326$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Haijuan</creatorcontrib><creatorcontrib>Rudge, Derek G.</creatorcontrib><creatorcontrib>Koos, Joseph D.</creatorcontrib><creatorcontrib>Vaidialingam, Bhamini</creatorcontrib><creatorcontrib>Yang, Hyo J.</creatorcontrib><creatorcontrib>Pavletich, Nikola P.</creatorcontrib><title>mTOR kinase structure, mechanism and regulation</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12–rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access.
In vitro
biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin–FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.
Structure of mTOR kinase
The mTOR (mammalian target of rapamycin) pathway is a central regulator of cell growth in response to environmental signals such as energy, nutrients and growth factors, and is misregulated in cancer and metabolic diseases. Here the first crystal structures of the mTOR kinase are presented. The 3.2 Å crystal structures of the enzyme bound to a positive regulator and to small-molecule ATP-competitive inhibitors reveal an intrinsically active kinase, and explain how the rapamycin–FKBP12 complex blocks recruitment of substrates to the kinase domain.</description><subject>631/45/275</subject><subject>631/535/1266</subject><subject>631/80/83/2359</subject><subject>631/80/86/2368</subject><subject>Adaptor Proteins, Signal Transducing - chemistry</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adenosine Triphosphate - chemistry</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>ATP</subject><subject>Catalytic Domain - drug effects</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Enzymes</subject><subject>Furans - chemistry</subject><subject>Furans - pharmacology</subject><subject>Growth factors</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Indoles - 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metabolism</subject><subject>Sirolimus - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Tacrolimus Binding Protein 1A - chemistry</subject><subject>Tacrolimus Binding Protein 1A - metabolism</subject><subject>Tacrolimus Binding Protein 1A - pharmacology</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>TOR Serine-Threonine Kinases - chemistry</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0M9LwzAUB_AgipvTk3cpeBFc3UvSJM1Rhr9gMJB5LmmazM42nUl78L-3ZVOGSA7vkA_f9_gidInhDgNNZ061nTeYYEKO0BgngscJT8UxGgOQNIaU8hE6C2EDAAyL5BSNCOX9I3yMZvVq-Rp9lE4FE4XWd3oIm0a10e_KlaGOlCsib9ZdpdqycefoxKoqmIv9nKC3x4fV_DleLJ9e5veLWFOJ25ixgnAhpFQy14mVWibAbUFAK8zznBGmsNDMkiTl1hqWSwNGcKIxlxKnlk7QzS5365vPzoQ2q8ugTVUpZ5ouZJgywIxQKXp6_Ydums67_rpBMQkc6KBud0r7JgRvbLb1Za38V4YhG3rMDnrs9dU-s8trU_zan-J6MN2B0H-5tfEHS__J-wZuj3u8</recordid><startdate>20130509</startdate><enddate>20130509</enddate><creator>Yang, Haijuan</creator><creator>Rudge, Derek G.</creator><creator>Koos, Joseph D.</creator><creator>Vaidialingam, Bhamini</creator><creator>Yang, Hyo J.</creator><creator>Pavletich, Nikola P.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope></search><sort><creationdate>20130509</creationdate><title>mTOR kinase structure, mechanism and regulation</title><author>Yang, Haijuan ; Rudge, Derek G. ; Koos, Joseph D. ; Vaidialingam, Bhamini ; Yang, Hyo J. ; Pavletich, Nikola P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-55d267799a9bc4f9c9406fd20ca16bb525a17c5f2486ffe5b9e0e762c169918f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/45/275</topic><topic>631/535/1266</topic><topic>631/80/83/2359</topic><topic>631/80/86/2368</topic><topic>Adaptor Proteins, Signal Transducing - chemistry</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Adenosine Triphosphate - chemistry</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>ATP</topic><topic>Catalytic Domain - drug effects</topic><topic>Crystal structure</topic><topic>Crystallography, X-Ray</topic><topic>Enzymes</topic><topic>Furans - chemistry</topic><topic>Furans - pharmacology</topic><topic>Growth factors</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Indoles - chemistry</topic><topic>Indoles - metabolism</topic><topic>Indoles - pharmacology</topic><topic>Kinases</topic><topic>Magnesium - chemistry</topic><topic>Magnesium - metabolism</topic><topic>Mammals</topic><topic>Models, Molecular</topic><topic>mTOR Associated Protein, LST8 Homolog</topic><topic>multidisciplinary</topic><topic>Naphthyridines - chemistry</topic><topic>Naphthyridines - metabolism</topic><topic>Naphthyridines - pharmacology</topic><topic>Protein Structure, Tertiary - drug effects</topic><topic>Proteins</topic><topic>Purines - chemistry</topic><topic>Purines - metabolism</topic><topic>Purines - pharmacology</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - pharmacology</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - pharmacology</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</topic><topic>Science</topic><topic>Sirolimus - chemistry</topic><topic>Sirolimus - metabolism</topic><topic>Sirolimus - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Tacrolimus Binding Protein 1A - chemistry</topic><topic>Tacrolimus Binding Protein 1A - metabolism</topic><topic>Tacrolimus Binding Protein 1A - pharmacology</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>TOR Serine-Threonine Kinases - chemistry</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Haijuan</creatorcontrib><creatorcontrib>Rudge, Derek G.</creatorcontrib><creatorcontrib>Koos, Joseph D.</creatorcontrib><creatorcontrib>Vaidialingam, Bhamini</creatorcontrib><creatorcontrib>Yang, Hyo J.</creatorcontrib><creatorcontrib>Pavletich, Nikola P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medicine (ProQuest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (ProQuest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Haijuan</au><au>Rudge, Derek G.</au><au>Koos, Joseph D.</au><au>Vaidialingam, Bhamini</au><au>Yang, Hyo J.</au><au>Pavletich, Nikola P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTOR kinase structure, mechanism and regulation</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2013-05-09</date><risdate>2013</risdate><volume>497</volume><issue>7448</issue><spage>217</spage><epage>223</epage><pages>217-223</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12–rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access.
In vitro
biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin–FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.
Structure of mTOR kinase
The mTOR (mammalian target of rapamycin) pathway is a central regulator of cell growth in response to environmental signals such as energy, nutrients and growth factors, and is misregulated in cancer and metabolic diseases. Here the first crystal structures of the mTOR kinase are presented. The 3.2 Å crystal structures of the enzyme bound to a positive regulator and to small-molecule ATP-competitive inhibitors reveal an intrinsically active kinase, and explain how the rapamycin–FKBP12 complex blocks recruitment of substrates to the kinase domain.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23636326</pmid><doi>10.1038/nature12122</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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recordid | cdi_proquest_miscellaneous_1350152397 |
source | MEDLINE; Nature Journals Online; Alma/SFX Local Collection |
subjects | 631/45/275 631/535/1266 631/80/83/2359 631/80/86/2368 Adaptor Proteins, Signal Transducing - chemistry Adaptor Proteins, Signal Transducing - metabolism Adenosine Triphosphate - chemistry Adenosine Triphosphate - metabolism ATP Catalytic Domain - drug effects Crystal structure Crystallography, X-Ray Enzymes Furans - chemistry Furans - pharmacology Growth factors Humanities and Social Sciences Humans Indoles - chemistry Indoles - metabolism Indoles - pharmacology Kinases Magnesium - chemistry Magnesium - metabolism Mammals Models, Molecular mTOR Associated Protein, LST8 Homolog multidisciplinary Naphthyridines - chemistry Naphthyridines - metabolism Naphthyridines - pharmacology Protein Structure, Tertiary - drug effects Proteins Purines - chemistry Purines - metabolism Purines - pharmacology Pyridines - chemistry Pyridines - pharmacology Pyrimidines - chemistry Pyrimidines - pharmacology Ribosomal Protein S6 Kinases, 70-kDa - metabolism Science Sirolimus - chemistry Sirolimus - metabolism Sirolimus - pharmacology Structure-Activity Relationship Tacrolimus Binding Protein 1A - chemistry Tacrolimus Binding Protein 1A - metabolism Tacrolimus Binding Protein 1A - pharmacology TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - chemistry TOR Serine-Threonine Kinases - metabolism |
title | mTOR kinase structure, mechanism and regulation |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T19%3A39%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=mTOR%20kinase%20structure,%20mechanism%20and%20regulation&rft.jtitle=Nature%20(London)&rft.au=Yang,%20Haijuan&rft.date=2013-05-09&rft.volume=497&rft.issue=7448&rft.spage=217&rft.epage=223&rft.pages=217-223&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature12122&rft_dat=%3Cproquest_cross%3E2982011551%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1355906037&rft_id=info:pmid/23636326&rfr_iscdi=true |