Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Mechanistic insight into substrate processing and allosteric inhibition of human p97.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 28, Issue 7, Page 614-625, Year 2021
Publish date	Jul 14, 2021
Authors	Man Pan / Yuanyuan Yu / Huasong Ai / Qingyun Zheng / Yuan Xie / Lei Liu / Minglei Zhao /
PubMed Abstract	p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with ...p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 Å that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 Å. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically.
External links	Nat Struct Mol Biol / PubMed:34262183
Methods	EM (single particle)
Resolution	2.4 - 6.0 Å
Structure data	23442 7lmy EMDB-23442, PDB-7lmy: Cryo-EM structure of human p97 in complex with NMS-873 in the presence of ATP, Npl4/Ufd1, and Ub6 Method: EM (single particle) / Resolution: 2.4 Å 23443 7lmz EMDB-23443, PDB-7lmz: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and Ub6 (Class 1) Method: EM (single particle) / Resolution: 3.06 Å 23444 7ln0 EMDB-23444, PDB-7ln0: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and Ub6 (Class 2) Method: EM (single particle) / Resolution: 2.98 Å 23445 7ln1 EMDB-23445, PDB-7ln1: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and Ub6 (Class 3) Method: EM (single particle) / Resolution: 3.4 Å 23446 7ln2 EMDB-23446, PDB-7ln2: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 1) Method: EM (single particle) / Resolution: 3.63 Å 23447 7ln3 EMDB-23447, PDB-7ln3: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 2) Method: EM (single particle) / Resolution: 3.45 Å 23448 7ln4 EMDB-23448, PDB-7ln4: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 3) Method: EM (single particle) / Resolution: 3.0 Å 23449 7ln5 EMDB-23449, PDB-7ln5: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (CHAPSO, Class 1, Close State) Method: EM (single particle) / Resolution: 3.09 Å 23450 7ln6 EMDB-23450, PDB-7ln6: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (CHAPSO, Class 2, Open State) Method: EM (single particle) / Resolution: 3.58 Å EMDB-23451: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (Class 3) Method: EM (single particle) / Resolution: 3.77 Å EMDB-23452: Human p97 in complex with NMS-873 in the presence of ATP, Npl4/Ufd1 and plyubiquitinated Ub-Eos Method: EM (single particle) / Resolution: 2.87 Å EMDB-23453: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 1) Method: EM (single particle) / Resolution: 3.69 Å EMDB-23454: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 2) Method: EM (single particle) / Resolution: 6.0 Å EMDB-23455: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 3) Method: EM (single particle) / Resolution: 3.58 Å EMDB-23456: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 4) Method: EM (single particle) / Resolution: 4.25 Å EMDB-23457: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 5) Method: EM (single particle) / Resolution: 3.47 Å EMDB-23458: Human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos in the presence of ATP and sub-stoichiometric NMS-873 (Class 6) Method: EM (single particle) / Resolution: 3.65 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM / Adenosine triphosphate ChemComp-Y6Y: 3-[3-cyclopentylsulfanyl-5-[[3-methyl-4-(4-methylsulfonylphenyl)phenoxy]methyl]-1,2,4-triazol-4-yl]pyridine ChemComp-MG: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM / Adenosine diphosphate
Source	homo sapiens (human) mus musculus (house mouse)
Keywords	TRANSLOCASE / p97 / NMS-873 / single-particle cryo-EM / translocation / allosteric inhibition