4MQT
 
 | | Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist iperoxo and allosteric modulator LY2119620 | | 分子名称: | 3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide, 4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium, Muscarinic acetylcholine receptor M2, ... | | 著者 | Kruse, A.C, Ring, A.M, Manglik, A, Hu, J, Hu, K, Eitel, K, Huebner, H, Pardon, E, Valant, C, Sexton, P.M, Christopoulos, A, Felder, C.C, Gmeiner, P, Steyaert, J, Weis, W.I, Garcia, K.C, Wess, J, Kobilka, B.K. | | 登録日 | 2013-09-16 | | 公開日 | 2013-11-27 | | 最終更新日 | 2024-11-06 | | 実験手法 | X-RAY DIFFRACTION (3.7 Å) | | 主引用文献 | Activation and allosteric modulation of a muscarinic acetylcholine receptor.
Nature, 504, 2013
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8P8J
 | | Structure of 5D3-Fab and nanobody(Nb96)-bound ABCG2 | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose, 5D3(Fab) heavy chain variable domain, 5D3(Fab) light chain variable domain, ... | | 著者 | Irobalieva, R.N, Manolaridis, I, Jackson, S.M, Ni, D, Pardon, E, Stahlberg, H, Steyaert, J, Locher, K.P. | | 登録日 | 2023-06-01 | | 公開日 | 2023-08-30 | | 最終更新日 | 2024-10-16 | | 実験手法 | ELECTRON MICROSCOPY (3.49 Å) | | 主引用文献 | Structural Basis of the Allosteric Inhibition of Human ABCG2 by Nanobodies.
J.Mol.Biol., 435, 2023
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8P7W
 | | Structure of 5D3-Fab and nanobody(Nb8)-bound ABCG2 | | 分子名称: | 5D3(Fab) heavy chain variable domain, 5D3(Fab) light chain variable domain, ATP-binding cassette sub-family G member 2, ... | | 著者 | Irobalieva, R.N, Manolaridis, I, Jackson, S.M, Ni, D, Pardon, E, Stahlberg, H, Steyaert, J, Locher, K.P. | | 登録日 | 2023-05-31 | | 公開日 | 2023-08-30 | | 最終更新日 | 2024-11-13 | | 実験手法 | ELECTRON MICROSCOPY (3.04 Å) | | 主引用文献 | Structural Basis of the Allosteric Inhibition of Human ABCG2 by Nanobodies.
J.Mol.Biol., 435, 2023
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8P8A
 | | Structure of 5D3-Fab and nanobody(Nb17)-bound ABCG2 | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 5D3(Fab) heavy chain variable domain, 5D3(Fab) light chain variable domain, ... | | 著者 | Irobalieva, R.N, Manolaridis, I, Jackson, S.M, Ni, D, Pardon, E, Stahlberg, H, Steyaert, J, Locher, K.P. | | 登録日 | 2023-05-31 | | 公開日 | 2023-08-30 | | 最終更新日 | 2025-07-02 | | 実験手法 | ELECTRON MICROSCOPY (3.2 Å) | | 主引用文献 | Structural Basis of the Allosteric Inhibition of Human ABCG2 by Nanobodies.
J.Mol.Biol., 435, 2023
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8QZ2
 | | Crystal structure of human two pore domain potassium ion channel TREK-2 (K2P10.1) in complex with an inhibitory nanobody (Nb61) | | 分子名称: | Nanobody 61, POTASSIUM ION, Potassium channel subfamily K member 10 | | 著者 | Baronina, A, Pike, A.C.W, Rodstrom, K.E.J, Ang, J, Bushell, S.R, Chalk, R, Mukhopadhyay, S.M.M, Pardon, E, Arrowsmith, C.H, Edwards, A.M, Bountra, C, Burgess-Brown, N.A, Tucker, S.J, Steyaert, J, Carpenter, E.P, Structural Genomics Consortium (SGC) | | 登録日 | 2023-10-26 | | 公開日 | 2024-05-29 | | 最終更新日 | 2024-11-20 | | 実験手法 | X-RAY DIFFRACTION (3.5 Å) | | 主引用文献 | Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.
Nat Commun, 15, 2024
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8QZ1
 | | Crystal structure of human two pore domain potassium ion channel TREK-2 (K2P10.1) in complex with a nanobody (Nb58) | | 分子名称: | Isoform B of Potassium channel subfamily K member 10, Nanobody 58, POTASSIUM ION | | 著者 | Rodstrom, K.E.J, Pike, A.C.W, Baronina, A, Ang, J, Bushell, S.R, Chalk, R, Mukhopadhyay, S.M.M, Pardon, E, Arrowsmith, C.H, Edwards, A.M, Bountra, C, Burgess-Brown, N.A, Tucker, S.J, Steyaert, J, Carpenter, E.P, Structural Genomics Consortium (SGC) | | 登録日 | 2023-10-26 | | 公開日 | 2024-05-29 | | 最終更新日 | 2024-11-06 | | 実験手法 | X-RAY DIFFRACTION (3.588 Å) | | 主引用文献 | Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.
Nat Commun, 15, 2024
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8QZ3
 | | Crystal structure of human two pore domain potassium ion channel TREK-2 (K2P10.1) in complex with an activatory nanobody (Nb67) | | 分子名称: | (4S)-2-METHYL-2,4-PENTANEDIOL, Nanobody 67, POTASSIUM ION, ... | | 著者 | Baronina, A, Pike, A.C.W, Rodstrom, K.E.J, Ang, J, Bushell, S.R, Chalk, R, Mukhopadhyay, S.M.M, Pardon, E, Arrowsmith, C.H, Edwards, A.M, Bountra, C, Burgess-Brown, N.A, Tucker, S.J, Steyaert, J, Carpenter, E.P, Structural Genomics Consortium (SGC) | | 登録日 | 2023-10-26 | | 公開日 | 2024-05-29 | | 最終更新日 | 2024-11-20 | | 実験手法 | X-RAY DIFFRACTION (2.4 Å) | | 主引用文献 | Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.
Nat Commun, 15, 2024
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8QZ4
 | | Crystal structure of human two pore domain potassium ion channel TREK-2 (K2P10.1) in complex with an activatory nanobody (Nb76) | | 分子名称: | BARIUM ION, CHOLESTEROL HEMISUCCINATE, Nanobody 76, ... | | 著者 | Rodstrom, K.E.J, Pike, A.C.W, Baronina, A, Ang, J, Bushell, S.R, Chalk, R, Mukhopadhyay, S.M.M, Pardon, E, Arrowsmith, C.H, Edwards, A.M, Bountra, C, Burgess-Brown, N.A, Tucker, S.J, Steyaert, J, Carpenter, E.P, Structural Genomics Consortium (SGC) | | 登録日 | 2023-10-26 | | 公開日 | 2024-05-29 | | 最終更新日 | 2024-11-06 | | 実験手法 | X-RAY DIFFRACTION (3.2 Å) | | 主引用文献 | Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.
Nat Commun, 15, 2024
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6HUK
 | | CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with bicuculline and megabody Mb38. | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, Gamma-aminobutyric acid receptor subunit alpha-1,Gamma-aminobutyric acid receptor subunit alpha-1, Gamma-aminobutyric acid receptor subunit beta-3, ... | | 著者 | Masiulis, S, Desai, R, Uchanski, T, Serna Martin, I, Laverty, D, Karia, D, Malinauskas, T, Jasenko, Z, Pardon, E, Kotecha, A, Steyaert, J, Miller, K.W, Aricescu, A.R. | | 登録日 | 2018-10-08 | | 公開日 | 2019-01-02 | | 最終更新日 | 2022-03-30 | | 実験手法 | ELECTRON MICROSCOPY (3.69 Å) | | 主引用文献 | GABAAreceptor signalling mechanisms revealed by structural pharmacology.
Nature, 565, 2019
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6I53
 | | Cryo-EM structure of the human synaptic alpha1-beta3-gamma2 GABAA receptor in complex with Megabody38 in a lipid nanodisc | | 分子名称: | (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, Gamma-aminobutyric acid receptor subunit alpha-1, ... | | 著者 | Laverty, D, Desai, R, Uchanski, T, Masiulis, S, Wojciech, J.S, Malinauskas, T, Zivanov, J, Pardon, E, Steyaert, J, Miller, K.W, Aricescu, A.R. | | 登録日 | 2018-11-12 | | 公開日 | 2019-01-02 | | 最終更新日 | 2024-10-23 | | 実験手法 | ELECTRON MICROSCOPY (3.2 Å) | | 主引用文献 | Cryo-EM structure of the human alpha 1 beta 3 gamma 2 GABAAreceptor in a lipid bilayer.
Nature, 565, 2019
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6HJX
 | | X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) 7'C pore mutant (L238C) in complex with nanobody 72 | | 分子名称: | 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, Cys-loop ligand-gated ion channel, DODECYL-BETA-D-MALTOSIDE, ... | | 著者 | Spurny, R, Govaerts, C, Evans, G.L, Pardon, E, Steyaert, J, Ulens, C. | | 登録日 | 2018-09-04 | | 公開日 | 2019-10-09 | | 最終更新日 | 2024-10-23 | | 実験手法 | X-RAY DIFFRACTION (2.5 Å) | | 主引用文献 | A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.
Nat.Chem.Biol., 15, 2019
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6HUP
 | | CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with diazepam (Valium), GABA and megabody Mb38. | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 7-CHLORO-1-METHYL-5-PHENYL-1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONE, GAMMA-AMINO-BUTANOIC ACID, ... | | 著者 | Masiulis, S, Desai, R, Uchanski, T, Serna Martin, I, Laverty, D, Karia, D, Malinauskas, T, Jasenko, Z, Pardon, E, Kotecha, A, Steyaert, J, Miller, K.W, Aricescu, A.R. | | 登録日 | 2018-10-09 | | 公開日 | 2019-01-02 | | 最終更新日 | 2024-11-13 | | 実験手法 | ELECTRON MICROSCOPY (3.58 Å) | | 主引用文献 | GABAAreceptor signalling mechanisms revealed by structural pharmacology.
Nature, 565, 2019
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6HUG
 | | CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with picrotoxin and megabody Mb38. | | 分子名称: | (1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-2a-hydroxy-8b-methyl-9-(prop-1-en-2-yl)hexahydro-3,6-methano-1,5,7-trioxacyclopenta[ij]c yclopropa[a]azulene-4,8(3H)-dione, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, Gamma-aminobutyric acid receptor subunit alpha-1, ... | | 著者 | Masiulis, S, Desai, R, Uchanski, T, Serna Martin, I, Laverty, D, Karia, D, Malinauskas, T, Jasenko, Z, Pardon, E, Kotecha, A, Steyaert, J, Miller, K.W, Aricescu, A.R. | | 登録日 | 2018-10-08 | | 公開日 | 2019-01-02 | | 最終更新日 | 2024-11-20 | | 実験手法 | ELECTRON MICROSCOPY (3.1 Å) | | 主引用文献 | GABAAreceptor signalling mechanisms revealed by structural pharmacology.
Nature, 565, 2019
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6HUO
 | | CryoEM structure of human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex with alprazolam (Xanax), GABA and megabody Mb38. | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine, GAMMA-AMINO-BUTANOIC ACID, ... | | 著者 | Masiulis, S, Desai, R, Uchanski, T, Serna Martin, I, Laverty, D, Karia, D, Malinauskas, T, Jasenko, Z, Pardon, E, Kotecha, A, Steyaert, J, Miller, K.W, Aricescu, A.R. | | 登録日 | 2018-10-09 | | 公開日 | 2019-01-02 | | 最終更新日 | 2024-11-06 | | 実験手法 | ELECTRON MICROSCOPY (3.26 Å) | | 主引用文献 | GABAAreceptor signalling mechanisms revealed by structural pharmacology.
Nature, 565, 2019
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6HJY
 | | X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) Delta8 truncation mutant in complex with nanobody 72 | | 分子名称: | Cys-loop ligand-gated ion channel, nanobody 72 | | 著者 | Spurny, R, Govaerts, C, Evans, G.L, Pardon, E, Steyaert, J, Ulens, C. | | 登録日 | 2018-09-04 | | 公開日 | 2019-10-09 | | 最終更新日 | 2024-10-23 | | 実験手法 | X-RAY DIFFRACTION (2.78 Å) | | 主引用文献 | A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.
Nat.Chem.Biol., 15, 2019
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6HUJ
 | | CryoEM structure of human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex with picrotoxin, GABA and megabody Mb38. | | 分子名称: | (1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-2a-hydroxy-8b-methyl-9-(prop-1-en-2-yl)hexahydro-3,6-methano-1,5,7-trioxacyclopenta[ij]c yclopropa[a]azulene-4,8(3H)-dione, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, GAMMA-AMINO-BUTANOIC ACID, ... | | 著者 | Masiulis, S, Desai, R, Uchanski, T, Serna Martin, I, Laverty, D, Karia, D, Malinauskas, T, Jasenko, Z, Pardon, E, Kotecha, A, Steyaert, J, Miller, K.W, Aricescu, A.R. | | 登録日 | 2018-10-08 | | 公開日 | 2019-01-02 | | 最終更新日 | 2024-10-16 | | 実験手法 | ELECTRON MICROSCOPY (3.04 Å) | | 主引用文献 | GABAAreceptor signalling mechanisms revealed by structural pharmacology.
Nature, 565, 2019
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6QFA
 | | CryoEM structure of a beta3K279T GABA(A)R homomer in complex with histamine and megabody Mb25 | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose, Gamma-aminobutyric acid receptor subunit beta-3,Gamma-aminobutyric acid receptor subunit beta-3, HISTAMINE, ... | | 著者 | Uchanski, T, Masiulis, S, Fischer, B, Kalichuk, V, Wohlkoening, A, Zoegg, T, Remaut, H, Vranken, W, Aricescu, A.R, Pardon, E, Steyaert, J. | | 登録日 | 2019-01-09 | | 公開日 | 2021-08-04 | | 最終更新日 | 2024-10-09 | | 実験手法 | ELECTRON MICROSCOPY (2.49 Å) | | 主引用文献 | Megabodies expand the nanobody toolkit for protein structure determination by single-particle cryo-EM.
Nat.Methods, 18, 2021
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6GCI
 | | Structure of the bongkrekic acid-inhibited mitochondrial ADP/ATP carrier | | 分子名称: | Bongkrekic acid, CARDIOLIPIN, HEXAETHYLENE GLYCOL, ... | | 著者 | Ruprecht, J.J, King, M.S, Pardon, E, Aleksandrova, A.A, Zogg, T, Crichton, P.G, Steyaert, J, Kunji, E.R.S. | | 登録日 | 2018-04-17 | | 公開日 | 2019-01-09 | | 最終更新日 | 2024-11-13 | | 実験手法 | X-RAY DIFFRACTION (3.3 Å) | | 主引用文献 | The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier.
Cell, 176, 2019
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6HK0
 | | X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) F16'S pore mutant (F247S) with alternate M4 conformation. | | 分子名称: | Cys-loop ligand-gated ion channel, DODECYL-BETA-D-MALTOSIDE | | 著者 | Nury, H, Spurny, R, Govaerts, C, Evans, G.L, Pardon, E, Steyaert, J, Ulens, C. | | 登録日 | 2018-09-04 | | 公開日 | 2019-10-09 | | 最終更新日 | 2024-01-17 | | 実験手法 | X-RAY DIFFRACTION (3.45 Å) | | 主引用文献 | A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.
Nat.Chem.Biol., 15, 2019
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9GIW
 | | Structure of the human mitochondrial pyruvate carrier inhibited by zaprinast | | 分子名称: | 5-(2-propoxyphenyl)-3,4-dihydro-[1,2,3]triazolo[4,5-d]pyrimidin-7-one, Mitochondrial pyruvate carrier 1-like protein, Mitochondrial pyruvate carrier 2, ... | | 著者 | Sichrovsky, M, Lacabanne, D, Ruprecht, J.J, Rana, J.J, Stanik, K, Dionysopoulou, M, Sowton, A.P, King, M.S, Jones, S, Cooper, L, Hardwick, S.W, Paris, G, Chirgadze, D.Y, Ding, S, Fearnley, I.M, Palmer, S, Pardon, E, Steyaert, J, Leone, V, Forrest, L.R, Tavoulari, S, Kunji, E.R.S. | | 登録日 | 2024-08-19 | | 公開日 | 2025-05-07 | | 実験手法 | ELECTRON MICROSCOPY (3.92 Å) | | 主引用文献 | Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.
Sci Adv, 11, 2025
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9GIV
 | | Structure of the human mitochondrial pyruvate carrier inhibited by a UK5099-derivative | | 分子名称: | (~{E})-2-cyano-3-[5-(2-nitrophenyl)furan-2-yl]prop-2-enoic acid, Mitochondrial pyruvate carrier 1-like protein, Mitochondrial pyruvate carrier 2, ... | | 著者 | Sichrovsky, M, Lacabanne, D, Ruprecht, J.J, Rana, J.J, Stanik, K, Dionysopoulou, M, Sowton, A.P, King, M.S, Jones, S, Cooper, L, Hardwick, S.W, Paris, G, Chirgadze, D.Y, Ding, S, Fearnley, I.M.F, Palmer, S, Pardon, E, Steyaert, J, Leone, V, Forrest, L.R, Tavoulari, S, Kunji, E.R.S. | | 登録日 | 2024-08-19 | | 公開日 | 2025-05-07 | | 実験手法 | ELECTRON MICROSCOPY (3.65 Å) | | 主引用文献 | Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.
Sci Adv, 11, 2025
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9GIY
 | | Structure of the human mitochondrial pyruvate carrier inhibited by mitoglitazone | | 分子名称: | Macrobody,Maltose/maltodextrin-binding periplasmic protein, Mitochondrial pyruvate carrier 1-like protein, Mitochondrial pyruvate carrier 2, ... | | 著者 | Sichrovsky, M, Lacabanne, D, Ruprecht, J.J, Rana, J.J, Stanik, K, Dionysopoulou, M, King, M.S, Sowton, A.P, Jones, S, Cooper, L, Hardwick, S.W, Paris, G, Chirgadze, D.Y, Ding, S, Fearnley, I.M, Palmer, S, Pardon, E, Steyaert, J, Leone, V, Forrest, L.R, Tavoulari, S, Kunji, E.R.S. | | 登録日 | 2024-08-19 | | 公開日 | 2025-05-07 | | 実験手法 | ELECTRON MICROSCOPY (3.79 Å) | | 主引用文献 | Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.
Sci Adv, 11, 2025
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9GIX
 | | Structure of the human mitochondrial pyruvate carrier in the apo-state | | 分子名称: | MBP-nanobody,Maltose/maltodextrin-binding periplasmic protein, Mitochondrial pyruvate carrier 1-like protein, Mitochondrial pyruvate carrier 2 | | 著者 | Sichrovsky, M, Lacabanne, D, Ruprecht, J.J, Rana, J.J, Stanik, K, Dionysopoulou, M, Sowton, A.P, King, M.S, Jones, S, Cooper, L, Hardwick, S.W, Paris, G, Chirgadze, D.Y, Ding, S, Fearnley, I.M, Palmer, S, Pardon, E, Steyaert, J, Leone, V, Forrest, L.R, Tavoulari, S, Kunji, E.R.S. | | 登録日 | 2024-08-19 | | 公開日 | 2025-05-07 | | 実験手法 | ELECTRON MICROSCOPY (3.65 Å) | | 主引用文献 | Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.
Sci Adv, 11, 2025
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9FZQ
 | | Proton conductance by human uncoupling protein 1 is inhibited by both purine and pyrimidine nucleotides | | 分子名称: | CA9865, CA9871, CARDIOLIPIN, ... | | 著者 | Jones, S.A, Sowton, A.P, Lacabanne, D, King, M.S, Palmer, S.M, Zogg, T, Pardon, E, Steyaert, J, Ruprecht, J.J, Kunji, E.R.S. | | 登録日 | 2024-07-05 | | 公開日 | 2025-03-05 | | 最終更新日 | 2025-07-02 | | 実験手法 | ELECTRON MICROSCOPY (3.03 Å) | | 主引用文献 | Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides.
Embo J., 44, 2025
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6RTW
 | | Crystal structure of the Patched-1 (PTCH1) ectodomain in complex with nanobody NB64 and cholesterol-hemisuccinate | | 分子名称: | 2-acetamido-2-deoxy-beta-D-glucopyranose, CHOLESTEROL HEMISUCCINATE, Llama-derived nanobody NB64, ... | | 著者 | Rudolf, A.F, Kowatsch, C, El Omari, K, Malinauskas, T, Kinnebrew, M, Ansell, T.B, Bishop, B, Pardon, E, Schwab, R.A, Qian, M, Duman, R, Covey, D.F, Steyaert, J, Wagner, A, Sansom, M.S.P, Rohatgi, R, Siebold, C. | | 登録日 | 2019-05-27 | | 公開日 | 2019-10-02 | | 最終更新日 | 2024-11-06 | | 実験手法 | X-RAY DIFFRACTION (1.9 Å) | | 主引用文献 | The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism.
Nat.Chem.Biol., 15, 2019
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