4AN9
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![BU of 4an9 by Molmil](/molmil-images/mine/4an9) | Crystal structures of human MEK1 with carboxamide-based allosteric inhibitor XL518 (GDC-0973), or related analogs. | Descriptor: | DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1, MAGNESIUM ION, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... | Authors: | Rice, K.D, Aay, N, Anand, N.K, Blazey, C.M, Bowles, O.J, Bussenius, J, Costanzo, S, Curtis, J.K, Defina, S.C, Dubenko, L, Engst, S, Joshi, A.A, Kennedy, A.R, Kim, A.I, Koltun, E.S, Lougheed, J.C, Manalo, J.C.L, Martini, J.F, Nuss, J.M, Peto, C.J, Tsang, T.H, Yu, P, Johnston, S. | Deposit date: | 2012-03-16 | Release date: | 2012-12-19 | Last modified: | 2024-05-01 | Method: | X-RAY DIFFRACTION (2.8 Å) | Cite: | Novel Carboxamide-Based Allosteric Mek Inhibitors: Discovery and Optimization Efforts Toward Xl518 (Gdc-0973) Acs Med.Chem.Lett., 3, 2012
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4LMN
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![BU of 4lmn by Molmil](/molmil-images/mine/4lmn) | Crystal Structure of MEK1 kinase bound to GDC0973 | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... | Authors: | Ultsch, M.H. | Deposit date: | 2013-07-10 | Release date: | 2013-08-07 | Last modified: | 2024-02-28 | Method: | X-RAY DIFFRACTION (2.8 Å) | Cite: | Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature, 501, 2013
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3ORN
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![BU of 3orn by Molmil](/molmil-images/mine/3orn) | Mitogen-activated protein kinase kinase 1 (MEK1) in complex with CH4987655 and MgAMP-PNP | Descriptor: | 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-5-[(3-oxo-1,2-oxazinan-2-yl)methyl]benzamide, Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, ... | Authors: | Lukacs, C.M, Janson, C, Schuck, V, Belunis, C. | Deposit date: | 2010-09-07 | Release date: | 2011-03-02 | Last modified: | 2024-02-21 | Method: | X-RAY DIFFRACTION (2.8 Å) | Cite: | Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent. Bioorg.Med.Chem.Lett., 21, 2011
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3OS3
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![BU of 3os3 by Molmil](/molmil-images/mine/3os3) | Mitogen-activated protein kinase kinase 1 (MEK1) in complex with CH4858061 and MgATP | Descriptor: | 2-[(4-ethynyl-2-fluorophenyl)amino]-3,4-difluoro-N-(2-hydroxyethoxy)-5-{[(2-hydroxyethoxy)imino]methyl}benzamide, ADENOSINE-5'-TRIPHOSPHATE, Dual specificity mitogen-activated protein kinase kinase 1, ... | Authors: | Lukacs, C.M, Janson, C, Schuck, V, Belunis, C. | Deposit date: | 2010-09-08 | Release date: | 2011-07-27 | Last modified: | 2024-02-21 | Method: | X-RAY DIFFRACTION (2.8 Å) | Cite: | Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent. Bioorg.Med.Chem.Lett., 21, 2011
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4U7Z
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![BU of 4u7z by Molmil](/molmil-images/mine/4u7z) | Mitogen-Activated Protein Kinase Kinase (MEK1) bound to G805 | Descriptor: | 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide, Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, ... | Authors: | Robarge, K.D, Ultsch, M.H, Wiesmann, C. | Deposit date: | 2014-07-31 | Release date: | 2014-09-24 | Last modified: | 2023-09-27 | Method: | X-RAY DIFFRACTION (2.805 Å) | Cite: | Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479. Bioorg.Med.Chem.Lett., 24, 2014
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9AXH
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![BU of 9axh by Molmil](/molmil-images/mine/9axh) | Crystal structure of KSR1/MEK1 complex heterotetramer with NST-628 | Descriptor: | 1,2-ETHANEDIOL, CHLORIDE ION, Dual specificity mitogen-activated protein kinase kinase 1, ... | Authors: | Quade, B, Huang, X. | Deposit date: | 2024-03-06 | Release date: | 2024-04-17 | Method: | X-RAY DIFFRACTION (2.81 Å) | Cite: | The pan-RAF-MEK non degrading molecular glue NST-628 is a potent and brain penetrant inhibitor of the RAS-MAPK pathway with activity across diverse RAS- and RAF-driven cancers. Cancer Discov, 2024
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4MNE
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![BU of 4mne by Molmil](/molmil-images/mine/4mne) | Crystal structure of the BRAF:MEK1 complex | Descriptor: | 7-fluoro-3-[(2-fluoro-4-iodophenyl)amino]-N-{[(2S)-2-hydroxypropyl]oxy}furo[3,2-c]pyridine-2-carboxamide, CHLORIDE ION, Dual specificity mitogen-activated protein kinase kinase 1, ... | Authors: | Sudhamsu, J, Haling, J.R, Morales, T, Brandhuber, B, Hymowitz, S.G. | Deposit date: | 2013-09-10 | Release date: | 2014-06-18 | Last modified: | 2023-09-20 | Method: | X-RAY DIFFRACTION (2.8483 Å) | Cite: | Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling. Cancer Cell, 26, 2014
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6U2G
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![BU of 6u2g by Molmil](/molmil-images/mine/6u2g) | BRAF-MEK complex with AMP-PCP bound to BRAF | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... | Authors: | Liau, N.P.D, Wendorff, T, Hymowitz, S, Sudhamsu, J. | Deposit date: | 2019-08-19 | Release date: | 2019-08-28 | Last modified: | 2023-10-11 | Method: | X-RAY DIFFRACTION (2.886 Å) | Cite: | Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization. Nat.Struct.Mol.Biol., 27, 2020
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5YT3
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![BU of 5yt3 by Molmil](/molmil-images/mine/5yt3) | Structure of the Human Mitogen-Activated Protein Kinase Kinase 1 S218D and S222D mutant | Descriptor: | MAGNESIUM ION, Mitogen-activated protein kinase kinase 1, isoform CRA_d, ... | Authors: | Nakae, S, Doko, K, Tada, T, Shirai, T. | Deposit date: | 2017-11-16 | Release date: | 2018-11-21 | Last modified: | 2023-11-22 | Method: | X-RAY DIFFRACTION (2.9 Å) | Cite: | Structure of the Human Mitogen-Activated Protein Kinase Kinase 1 S218D and S222D mutant To Be Published
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5BX0
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![BU of 5bx0 by Molmil](/molmil-images/mine/5bx0) | |
7M0W
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![BU of 7m0w by Molmil](/molmil-images/mine/7m0w) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Pimasertib | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]pyridine-4-carboxamide, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Ha, B.H, Park, E, Eck, M.J. | Deposit date: | 2021-03-11 | Release date: | 2021-04-21 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (3.09 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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7M0U
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![BU of 7m0u by Molmil](/molmil-images/mine/7m0u) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Binimetinib | Descriptor: | 5-[(4-bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide, Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Ha, B.H, Park, E, Eck, M.J. | Deposit date: | 2021-03-11 | Release date: | 2021-04-21 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (3.09 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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6V2W
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![BU of 6v2w by Molmil](/molmil-images/mine/6v2w) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Park, E, Eck, M.J. | Deposit date: | 2019-11-25 | Release date: | 2020-12-02 | Last modified: | 2023-10-11 | Method: | X-RAY DIFFRACTION (3.12 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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7M0Z
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![BU of 7m0z by Molmil](/molmil-images/mine/7m0z) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and CH5126766 | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, N-(3-fluoro-4-{[4-methyl-2-oxo-7-(pyrimidin-2-yloxy)-2H-chromen-3-yl]methyl}pyridin-2-yl)-N'-methylsulfuric diamide, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Ha, B.H, Park, E, Eck, M.J. | Deposit date: | 2021-03-11 | Release date: | 2021-04-21 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (3.12 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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7M0V
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![BU of 7m0v by Molmil](/molmil-images/mine/7m0v) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Cobimetinib | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Ha, B.H, Park, E, Eck, M.J. | Deposit date: | 2021-03-11 | Release date: | 2021-04-21 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (3.16 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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7M0T
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![BU of 7m0t by Molmil](/molmil-images/mine/7m0t) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Selumetinib | Descriptor: | 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide, Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Ha, B.H, Park, E, Eck, M.J. | Deposit date: | 2021-03-11 | Release date: | 2021-04-21 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (3.19 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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7UMB
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![BU of 7umb by Molmil](/molmil-images/mine/7umb) | NanoBRET tracer Tram-bo bound to a KSR2-MEK1 complex | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, Kinase suppressor of Ras 2, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... | Authors: | Marsiglia, W.M, Khan, K.M, Dar, A.C. | Deposit date: | 2022-04-06 | Release date: | 2023-09-27 | Last modified: | 2024-03-20 | Method: | X-RAY DIFFRACTION (3.231 Å) | Cite: | Live-cell target engagement of allosteric MEKi on MEK-RAF/KSR-14-3-3 complexes. Nat.Chem.Biol., 20, 2024
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7M0Y
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![BU of 7m0y by Molmil](/molmil-images/mine/7m0y) | Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Trametinib | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... | Authors: | Li, K, Gonzalez Del-Pino, G, Ha, B.H, Park, E, Eck, M.J. | Deposit date: | 2021-03-11 | Release date: | 2021-04-21 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (3.45 Å) | Cite: | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc.Natl.Acad.Sci.USA, 118, 2021
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9AXY
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![BU of 9axy by Molmil](/molmil-images/mine/9axy) | Crystal structure of BRAF/MEK complex with NST-628 and inactive RAF | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, N-[3-fluoro-4-({7-[(3-fluoropyridin-2-yl)oxy]-4-methyl-2-oxo-2H-1-benzopyran-3-yl}methyl)pyridin-2-yl]-N'-methylsulfuric diamide, ... | Authors: | Quade, B, Huang, X. | Deposit date: | 2024-03-06 | Release date: | 2024-04-17 | Method: | X-RAY DIFFRACTION (3.6 Å) | Cite: | The pan-RAF-MEK non degrading molecular glue NST-628 is a potent and brain penetrant inhibitor of the RAS-MAPK pathway with activity across diverse RAS- and RAF-driven cancers. Cancer Discov, 2024
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7MFD
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![BU of 7mfd by Molmil](/molmil-images/mine/7mfd) | Autoinhibited BRAF:(14-3-3)2:MEK complex with the BRAF RBD resolved | Descriptor: | 14-3-3 protein zeta/delta, Dual specificity mitogen-activated protein kinase kinase 1, N-(3-fluoro-4-{[4-methyl-2-oxo-7-(pyrimidin-2-yloxy)-2H-chromen-3-yl]methyl}pyridin-2-yl)-N'-methylsulfuric diamide, ... | Authors: | Martinez Fiesco, J.A, Ping, Z, Durrant, D.E, Morrison, D.K. | Deposit date: | 2021-04-09 | Release date: | 2022-01-26 | Last modified: | 2022-02-09 | Method: | ELECTRON MICROSCOPY (3.66 Å) | Cite: | Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding. Nat Commun, 13, 2022
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8DGT
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![BU of 8dgt by Molmil](/molmil-images/mine/8dgt) | Cryo-EM structure of a RAS/RAF complex (state 2) | Descriptor: | 14-3-3 protein zeta, 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide, Dual specificity mitogen-activated protein kinase kinase 1, ... | Authors: | Eck, M.J, Jeon, H, Park, E, Rawson, S. | Deposit date: | 2022-06-24 | Release date: | 2023-07-05 | Last modified: | 2023-08-09 | Method: | ELECTRON MICROSCOPY (3.9 Å) | Cite: | Cryo-EM structure of a RAS/RAF recruitment complex. Nat Commun, 14, 2023
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6NYB
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![BU of 6nyb by Molmil](/molmil-images/mine/6nyb) | Structure of a MAPK pathway complex | Descriptor: | 14-3-3 protein zeta, 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide, ADENOSINE-5'-DIPHOSPHATE, ... | Authors: | Park, E, Rawson, S, Li, K, Jeon, H, Eck, M.J. | Deposit date: | 2019-02-11 | Release date: | 2019-10-09 | Last modified: | 2020-04-22 | Method: | ELECTRON MICROSCOPY (4.1 Å) | Cite: | Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature, 575, 2019
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9AXC
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![BU of 9axc by Molmil](/molmil-images/mine/9axc) | Activated CRAF/MEK heterotetramer from focused refinement of CRAF/MEK/14-3-3 complex | Descriptor: | Dual specificity mitogen-activated protein kinase kinase 1, GST26/CRAF chimera, N-[3-fluoro-4-({7-[(3-fluoropyridin-2-yl)oxy]-4-methyl-2-oxo-2H-1-benzopyran-3-yl}methyl)pyridin-2-yl]-N'-methylsulfuric diamide | Authors: | Quade, B, Cohen, S.E, Huang, X. | Deposit date: | 2024-03-06 | Release date: | 2024-04-17 | Method: | ELECTRON MICROSCOPY (4.16 Å) | Cite: | The pan-RAF-MEK non degrading molecular glue NST-628 is a potent and brain penetrant inhibitor of the RAS-MAPK pathway with activity across diverse RAS- and RAF-driven cancers. Cancer Discov, 2024
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8CHF
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![BU of 8chf by Molmil](/molmil-images/mine/8chf) | cryo-EM Structure of Craf:14-3-3:Mek1 | Descriptor: | 14-3-3 protein zeta isoform X1, 2-{4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridin-4-yl)-1H-pyrazol-1-yl}ethanol, Dual specificity mitogen-activated protein kinase kinase 1, ... | Authors: | Dedden, D, Ulrich, G. | Deposit date: | 2023-02-07 | Release date: | 2024-02-21 | Last modified: | 2024-02-28 | Method: | ELECTRON MICROSCOPY (4.25 Å) | Cite: | Cryo-EM Structures of CRAF 2 /14-3-3 2 and CRAF 2 /14-3-3 2 /MEK1 2 Complexes. J.Mol.Biol., 436, 2024
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8DGS
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![BU of 8dgs by Molmil](/molmil-images/mine/8dgs) | Cryo-EM structure of a RAS/RAF complex (state 1) | Descriptor: | 14-3-3 protein zeta, 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide, Dual specificity mitogen-activated protein kinase kinase 1, ... | Authors: | Eck, M.J, Jeon, H, Park, E, Rawson, S. | Deposit date: | 2022-06-24 | Release date: | 2023-07-05 | Last modified: | 2023-08-09 | Method: | ELECTRON MICROSCOPY (4.3 Å) | Cite: | Cryo-EM structure of a RAS/RAF recruitment complex. Nat Commun, 14, 2023
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