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	A common mechanism of Sec61 translocon inhibition by small molecules.
Journal, issue, pages	Nat Chem Biol, Vol. 19, Issue 9, Page 1063-1071, Year 2023
Publish date	May 11, 2023
Authors	Samuel Itskanov / Laurie Wang / Tina Junne / Rumi Sherriff / Li Xiao / Nicolas Blanchard / Wei Q Shi / Craig Forsyth / Dominic Hoepfner / Martin Spiess / Eunyong Park /
PubMed Abstract	The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural ...The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural and synthetic small molecules specifically inhibit Sec61, generating cellular effects that are useful for therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures of human Sec61 inhibited by a comprehensive panel of structurally distinct small molecules-cotransin, decatransin, apratoxin, ipomoeassin, mycolactone, cyclotriazadisulfonamide and eeyarestatin. All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening. Our study provides the atomic details of Sec61-inhibitor interactions and the structural framework for further pharmacological studies and drug design.
External links	Nat Chem Biol / PubMed:37169959
Methods	EM (single particle)
Resolution	2.54 - 3.4 Å
Structure data	27581 8dnv EMDB-27581, PDB-8dnv: Cryo-EM structure of the human Sec61 complex in a partially-open apo state (Class 1) Method: EM (single particle) / Resolution: 3.03 Å 27582 8dnw EMDB-27582, PDB-8dnw: Cryo-EM structure of the human Sec61 complex in a partially-open apo state (Class 2) Method: EM (single particle) / Resolution: 3.4 Å 27583 8dnx EMDB-27583, PDB-8dnx: Cryo-EM structure of the human Sec61 complex inhibited by cotransin Method: EM (single particle) / Resolution: 2.98 Å 27584 8dny EMDB-27584, PDB-8dny: Cryo-EM structure of the human Sec61 complex inhibited by decatransin Method: EM (single particle) / Resolution: 2.85 Å 27585 8dnz EMDB-27585, PDB-8dnz: Cryo-EM structure of the human Sec61 complex inhibited by apratoxin F Method: EM (single particle) / Resolution: 2.57 Å 27586 8do0 EMDB-27586, PDB-8do0: Cryo-EM structure of the human Sec61 complex inhibited by mycolactone Method: EM (single particle) / Resolution: 2.86 Å 27587 8do1 EMDB-27587, PDB-8do1: Cryo-EM structure of the human Sec61 complex inhibited by ipomoeassin F Method: EM (single particle) / Resolution: 3.01 Å 27588 8do2 EMDB-27588, PDB-8do2: Cryo-EM structure of the human Sec61 complex inhibited by cyclotriazadisulfonamide (CADA) Method: EM (single particle) / Resolution: 2.95 Å 27589 8do3 EMDB-27589, PDB-8do3: Cryo-EM structure of the human Sec61 complex inhibited by eeyarestatin I Method: EM (single particle) / Resolution: 3.22 Å EMDB-29608: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by eeyarestatin I Method: EM (single particle) / Resolution: 2.79 Å EMDB-29609: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by cotransin Method: EM (single particle) / Resolution: 2.77 Å EMDB-29610: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by apratoxin F Method: EM (single particle) / Resolution: 2.54 Å EMDB-29611: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) in a partially-open apo state (Class 1) Method: EM (single particle) / Resolution: 2.74 Å EMDB-29612: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) in a partially-open apo state (Class 2) Method: EM (single particle) / Resolution: 2.84 Å EMDB-29613: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by decatransin Method: EM (single particle) / Resolution: 2.61 Å EMDB-29614: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by ipomoeassin F (Class 1) Method: EM (single particle) / Resolution: 2.9 Å EMDB-29616: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by cyclotriazadisulfonamide (CADA) Method: EM (single particle) / Resolution: 2.85 Å EMDB-29617: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by mycolactone Method: EM (single particle) / Resolution: 2.94 Å EMDB-29635: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by ipomoeassin F (Class 2) Method: EM (single particle) / Resolution: 2.7 Å
Chemicals	ChemComp-Q6B: [(6~{S},7~{S},9~{Z},12~{R})-12-[(~{Z},2~{S},6~{R},7~{R},9~{R})-4,6-dimethyl-7,9-bis(oxidanyl)dec-4-en-2-yl]-7,9-dimethyl-2-oxidanylidene-1-oxacyclododec-9-en-6-yl] (2~{E},4~{E},6~{E},8~{E},10~{E},12~{S},13~{S},15~{S})-4,6,10-trimethyl-12,13,15-tris(oxidanyl)hexadeca-2,4,6,8,10-pentaenoate ChemComp-HOH: WATER / Water ChemComp-SXF: [(1~{S},3~{R},4~{S},5~{R},6~{R},8~{R},10~{S},23~{R},24~{R},25~{R},26~{R})-5-acetyloxy-6-methyl-4,26-bis(oxidanyl)-17,20-bis(oxidanylidene)-10-pentyl-24-[(~{E})-3-phenylprop-2-enoyl]oxy-2,7,9,21,27-pentaoxatricyclo[21.3.1.0^{3,8}]heptacosan-25-yl] (~{E})-2-methylbut-2-enoate ChemComp-SXU: 9-benzyl-1,5-bis(4-methylbenzene-1-sulfonyl)-3-methylidene-1,5,9-triazacyclododecane ChemComp-SWR: N'-(4-chlorophenyl)-N-[(4R)-3-(4-chlorophenyl)-5,5-dimethyl-1-(2-{(2E)-2-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]hydrazinyl}-2-oxoethyl)-2-oxoimidazolidin-4-yl]-N-hydroxyurea
Source	homo sapiens (human) synthetic construct (others) lyngbya bouillonii (bacteria) Saccharomyces cerevisiae (brewer's yeast) Saccharomyces cerevisiae 'var. diastaticus' (brewer's yeast)
Keywords	PROTEIN TRANSPORT/INHIBITOR / translocon / inhibitor / protein translocation / PROTEIN TRANSPORT / PROTEIN TRANSPORT-INHIBITOR complex / decatransin