2I7N

Crystal structure of human PANK1 alpha: the catalytic core domain in complex with AcCoA

2I7N の概要

• エントリーDOI: 10.2210/pdb2i7n/pdb
• 関連するPDBエントリー: 2I7P
• 分子名称: Pantothenate kinase 1, ACETYL COENZYME *A (3 entities in total)
• 機能のキーワード: pank, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q8TE04
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81971.52

構造登録者

Hong, B.S.,Wang, L.,Tempel, W.,Loppnau, P.,Allali-Hassani, A.,Arrowsmith, C.H.,Edwards, A.M.,Sundstrom, M.,Weigelt, J.,Bochkarev, A.,Park, H.W. (登録日: 2006-08-31, 公開日: 2006-12-26, 最終更新日: 2024-02-21)

主引用文献

Hong, B.S.,Senisterra, G.,Rabeh, W.M.,Vedadi, M.,Leonardi, R.,Zhang, Y.M.,Rock, C.O.,Jackowski, S.,Park, H.W.
Crystal structures of human pantothenate kinases. Insights into allosteric regulation and mutations linked to a neurodegeneration disorder.
J.Biol.Chem., 282:27984-27993, 2007

PubMed Abstract: Pantothenate kinase (PanK) catalyzes the first step in CoA biosynthesis and there are three human genes that express four isoforms with highly conserved catalytic core domains. Here we report the homodimeric structures of the catalytic cores of PanK1alpha and PanK3 in complex with acetyl-CoA, a feedback inhibitor. Each monomer adopts a fold of the actin kinase superfamily and the inhibitor-bound structures explain the basis for the allosteric regulation by CoA thioesters. These structures also provide an opportunity to investigate the structural effects of the PanK2 mutations that have been implicated in neurodegeneration. Biochemical and thermodynamic analyses of the PanK3 mutant proteins corresponding to PanK2 mutations show that mutant proteins with compromised activities and/or stabilities correlate with a higher incidence of the early onset of disease.

PubMed: 17631502
DOI: 10.1074/jbc.M701915200

実験手法

X-RAY DIFFRACTION (1.9 Å)