9D4A

Atomic model of Ketoacyl Reductase domain and 4 helical bundle of S. cerevisiae Fatty Acid Synthase (FAS) in complex with octanoyl-CoA (in vitro binding)

これはPDB形式変換不可エントリーです。

9D4A の概要

• エントリーDOI: 10.2210/pdb9d4a/pdb
• EMDBエントリー: 46555
• 分子名称: Fatty acid synthase subunit beta, Fatty acid synthase subunit alpha, FLAVIN MONONUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: octanoyl-coa, fas, allosteric inhibition, biosynthetic protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 2621588.98

構造登録者

Hasan, N.S.M.,Keszei, F.A.A.,Mazhab-Jafari, M.T. (登録日: 2024-08-12, 公開日: 2025-08-20, 最終更新日: 2025-12-17)

主引用文献

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, 33:2041-2048.e4, 2025

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: 41043416
DOI: 10.1016/j.str.2025.09.005

実験手法

ELECTRON MICROSCOPY (2.61 Å)