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	Snapshots of acyl carrier protein shuttling in human fatty acid synthase.
Journal, issue, pages	Nature, Vol. 641, Issue 8062, Page 520-528, Year 2025
Publish date	Feb 20, 2025
Authors	Kollin Schultz / Pedro Costa-Pinheiro / Lauren Gardner / Laura V Pinheiro / Julio Ramirez-Solis / Sarah M Gardner / Kathryn E Wellen / Ronen Marmorstein /
PubMed Abstract	The mammalian fatty acid synthase (FASN) enzyme is a dynamic multienzyme that belongs to the megasynthase family. In mammals, a single gene encodes six catalytically active domains and a flexibly ...The mammalian fatty acid synthase (FASN) enzyme is a dynamic multienzyme that belongs to the megasynthase family. In mammals, a single gene encodes six catalytically active domains and a flexibly tethered acyl carrier protein (ACP) domain that shuttles intermediates between active sites for fatty acid biosynthesis. FASN is an essential enzyme in mammalian development through the role that fatty acids have in membrane formation, energy storage, cell signalling and protein modifications. Thus, FASN is a promising target for treatment of a large variety of diseases including cancer, metabolic dysfunction-associated fatty liver disease, and viral and parasite infections. The multi-faceted mechanism of FASN and the dynamic nature of the protein, in particular of the ACP, have made it challenging to understand at the molecular level. Here we report cryo-electron microscopy structures of human FASN in a multitude of conformational states with NADPH and NADP plus acetoacetyl-CoA present, including structures with the ACP stalled at the dehydratase (DH) and enoyl-reductase (ER) domains. We show that FASN activity in vitro and de novo lipogenesis in cells is inhibited by mutations at the ACP-DH and ACP-ER interfaces. Together, these studies provide new molecular insights into the dynamic nature of FASN and the ACP shuttling mechanism, with implications for developing improved FASN-targeted therapeutics.
External links	Nature / PubMed:39979457 / PubMed Central
Methods	EM (single particle)
Resolution	3.11 - 3.66 Å
Structure data	43187 8vf7 EMDB-43187, PDB-8vf7: Modifying portion of human FASN with NADPH and the ACP at the ER domain Method: EM (single particle) / Resolution: 3.2 Å 43199 8vg4 EMDB-43199, PDB-8vg4: Modifying portion of human FASN with NADPH and the ACP at the DH domain Method: EM (single particle) / Resolution: 3.11 Å 43337 8vle EMDB-43337, PDB-8vle: Composite structure of human FASN with NADPH in State 1 Method: EM (single particle) / Resolution: 3.3 Å 43340 8vlo EMDB-43340, PDB-8vlo: Composite structure of human FASN with NADPH in State 2 Method: EM (single particle) / Resolution: 3.3 Å 43341 8vlp EMDB-43341, PDB-8vlp: Composite structure of human FASN with NADPH in State 3 Method: EM (single particle) / Resolution: 3.2 Å 43350 8vm0 EMDB-43350, PDB-8vm0: Composite structure of human FASN with NADPH in State 4 Method: EM (single particle) / Resolution: 3.3 Å 43352 8vm5 EMDB-43352, PDB-8vm5: Composite structure of human FASN with NADPH in State 5 Method: EM (single particle) / Resolution: 3.3 Å 43353 8vm6 EMDB-43353, PDB-8vm6: Composite structure of human FASN with NADPH in State 8 Method: EM (single particle) / Resolution: 3.5 Å 43354 8vm7 EMDB-43354, PDB-8vm7: Composite structure of human FASN with NADPH in State 7 Method: EM (single particle) / Resolution: 3.3 Å 43355 8vmc EMDB-43355, PDB-8vmc: Composite structure of human FASN with NADPH in State 6 Method: EM (single particle) / Resolution: 3.3 Å 43356 8vmd EMDB-43356, PDB-8vmd: Modifying portion of human FASN with NADP+ and the ACP at the DH domain Method: EM (single particle) / Resolution: 3.46 Å EMDB-43414: Consensus map of hFASN/NADPH State 1 Method: EM (single particle) / Resolution: 3.63 Å EMDB-43415: Focused map of the modifying region of hFASN/NADPH State 1 Method: EM (single particle) / Resolution: 3.31 Å EMDB-43417: Focused map of the condensing region of hFASN/NADPH State 1 Method: EM (single particle) / Resolution: 3.27 Å EMDB-43441: Consensus map of hFASN/NADPH State 5 Method: EM (single particle) / Resolution: 3.29 Å EMDB-43442: Focused map of the modifying region of hFASN/NADPH State 5 Method: EM (single particle) / Resolution: 3.23 Å EMDB-43445: Focused map of the condensing region of hFASN/NADPH State 5 Method: EM (single particle) / Resolution: 3.44 Å EMDB-43447: Consensus map of hFASN/NADPH State 3 Method: EM (single particle) / Resolution: 3.35 Å EMDB-43448: Focused map of the modifying region of hFASN/NADPH State 3 Method: EM (single particle) / Resolution: 3.22 Å EMDB-43449: Focused map of the condensing region of hFASN/NADPH State 3 Method: EM (single particle) / Resolution: 3.18 Å EMDB-43454: Consensus map of hFASN/NADPH State 7 Method: EM (single particle) / Resolution: 3.45 Å EMDB-43456: Focused map of the modifying region of hFASN/NADPH State 7 Method: EM (single particle) / Resolution: 3.28 Å EMDB-43457: Focused map of the condensing region of hFASN/NADPH State 7 Method: EM (single particle) / Resolution: 3.27 Å EMDB-43458: Consensus map of hFASN/NADPH State 2 Method: EM (single particle) / Resolution: 3.65 Å EMDB-43459: Focused map of the modifying region of hFASN/NADPH State 2 Method: EM (single particle) / Resolution: 3.32 Å EMDB-43465: Focused map of the condensing region of hFASN/NADPH State 2 Method: EM (single particle) / Resolution: 3.22 Å EMDB-43466: Consensus map of hFASN/NADPH State 4 Method: EM (single particle) / Resolution: 3.58 Å EMDB-43467: Focused map of the modifying region of hFASN/NADPH State 4 Method: EM (single particle) / Resolution: 3.3 Å EMDB-43468: Focused map of the condensing region of hFASN/NADPH State 4 Method: EM (single particle) / Resolution: 3.29 Å EMDB-43469: Consensus map of hFASN/NADPH State 6 Method: EM (single particle) / Resolution: 3.28 Å EMDB-43470: Focused map of the modifying region of hFASN/NADPH State 6 Method: EM (single particle) / Resolution: 3.19 Å EMDB-43471: Focused map of the condensing region of hFASN/NADPH State 6 Method: EM (single particle) / Resolution: 3.31 Å EMDB-43472: Consensus map of hFASN/NADPH State 8 Method: EM (single particle) / Resolution: 3.6 Å EMDB-43473: Focused map of the modifying region of hFASN/NADPH State 8 Method: EM (single particle) / Resolution: 3.36 Å EMDB-43474: Focus map of the condensing region of hFASN/NADPH State 8 Method: EM (single particle) / Resolution: 3.66 Å
Chemicals	ChemComp-NDP: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE ChemComp-NAP: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
Source	homo sapiens (human)
Keywords	BIOSYNTHETIC PROTEIN / Megasynthase / Lipogenesis