9D49
Atomic model of triple mutant S. cerevisiae Fatty Acid Synthase (FAS) in complex with Palmitoyl-CoA (in vitro binding)
This is a non-PDB format compatible entry.
Summary for 9D49
| Entry DOI | 10.2210/pdb9d49/pdb |
| EMDB information | 46554 |
| Descriptor | Fatty acid synthase subunit beta, Fatty acid synthase subunit alpha, FLAVIN MONONUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | palmitoyl-coa, fas, allosteric inhibition, biosynthetic protein |
| Biological source | Saccharomyces cerevisiae (brewer's yeast) More |
| Total number of polymer chains | 12 |
| Total formula weight | 2625522.50 |
| Authors | Hasan, N.S.M.,Keszei, F.A.A.,Mazhab-Jafari, M.T. (deposition date: 2024-08-12, release date: 2025-08-27, Last modification date: 2025-10-15) |
| Primary citation | Hasan, S.M.N.,Samani, E.K.,Keszei, A.F.A.,Heydari, M.,Mazhab-Jafari, M.T. Allosteric regulation of fungal fatty acid synthesis. Structure, 2025 Cited by PubMed Abstract: Mycobiota fatty acid synthases (FASs) catalyze iterative cycles of condensation, dehydration, and reduction to produce saturated fatty acids. Although these multienzymes are attractive antifungal drug targets, no clinically approved small-molecule inhibitors exist, and the regulation of de novo fatty acid synthesis remains poorly understood. Here, we identify an allosteric regulation of the FAS ketoacyl reduction reaction by palmitoyl-CoA. The palmitate moiety binds a distal site on the central wheel of fungal FAS from Saccharomyces cerevisiae and Candida albicans. This site also accommodates shorter acyl chains, but only palmitoyl-CoA suppresses ketoacyl reductase (KR) activity. While no major conformational changes occur in the reductase domain, palmitoyl-CoA binding quenches dynamics in the central disk, improving local resolution and stabilizing structured water molecules. This entropic effect underlies allosteric communication to the reductase site. Our findings uncover a regulatory mechanism of fungal FAS exploitable for antifungal drug design. PubMed: 41043416DOI: 10.1016/j.str.2025.09.005 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.65 Å) |
Structure validation
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