2IWY

Human mitochondrial beta-ketoacyl ACP synthase

2IWY の概要

• エントリーDOI: 10.2210/pdb2iwy/pdb
• 関連するPDBエントリー: 2C9H 2IWZ 2IX4
• 分子名称: 3-OXOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE, AMMONIUM ION (3 entities in total)
• 機能のキーワード: mitochondria, mitochondrion, lipid synthesis, fatty acid synthesis, fatty acid biosynthesis, beta-ketoacyl acp synthase, transit peptide, acyltransferase, claisen condensation, kas, cerulenin, transferase, homo sapiens
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion : Q9NWU1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92915.21

構造登録者

Christensen, C.E.,Kragelund, B.B.,von Wettstein-Knowles, P.,Henriksen, A. (登録日: 2006-07-05, 公開日: 2007-02-06, 最終更新日: 2023-12-13)

主引用文献

Christensen, C.E.,Kragelund, B.B.,von Wettstein-Knowles, P.,Henriksen, A.
Structure of the Human Beta-Ketoacyl [Acp] Synthase from the Mitochondrial Type II Fatty Acid Synthase.
Protein Sci., 16:261-272, 2007

PubMed Abstract: Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual activities encoded by discrete genes. The beta-ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted by the antibiotic cerulenin and possibly by the other antibiotics inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the alpha-methylene butyrolactone, C75. The high degree of structural similarity between mitochondrial and prokaryotic KASes complicates development of novel antibiotics targeting prokaryotic KAS without affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic triad. Three KASes with different substrate specificities participate in synthesis of the C(16) and C(18) products of prokaryotic FAS. By comparison, mtKAS carries out all elongation reactions in the mitochondria. We present the X-ray crystal structures of the Cys-His-His-containing human mtKAS and its hexanoyl complex plus the hexanoyl complex of the plant mtKAS from Arabidopsis thaliana. The structures explain (1) the bimodal (C(6) and C(10)-C(12)) substrate preferences leading to the C(8) lipoic acid precursor and long chains for the membranes, respectively, and (2) the low cerulenin sensitivity of the human enzyme; and (3) reveal two different potential acyl-binding-pocket extensions. Rearrangements taking place in the active site, including subtle changes in the water network, indicate a change in cooperativity of the active-site histidines upon primer binding.

PubMed: 17242430
DOI: 10.1110/PS.062473707

実験手法

X-RAY DIFFRACTION (2.06 Å)