4GI7

Crystal structure of Klebsiella pneumoniae pantothenate kinase in complex with a pantothenate analogue

4GI7 の概要

• エントリーDOI: 10.2210/pdb4gi7/pdb
• 関連するPDBエントリー: 4F7W
• 関連するBIRD辞書のPRD_ID: PRD_000903
• 分子名称: Pantothenate kinase, ADENOSINE-5'-DIPHOSPHATE, (2R)-2,4-dihydroxy-3,3-dimethyl-N-{3-oxo-3-[(pyridin-3-ylmethyl)amino]propyl}butanamide, ... (5 entities in total)
• 機能のキーワード: protein-substrate complex, transferase, structural genomics, structural genomics consortium, sgc
• 由来する生物種: Klebsiella pneumoniae
• 細胞内の位置: Cytoplasm (By similarity): B5XYG3
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 312650.69

構造登録者

Li, B.,Tempel, W.,Smil, D.,Bolshan, Y.,Hong, B.S.,Park, H.W.,Structural Genomics Consortium (SGC) (登録日: 2012-08-08, 公開日: 2013-04-10, 最終更新日: 2024-02-28)

主引用文献

Li, B.,Tempel, W.,Smil, D.,Bolshan, Y.,Schapira, M.,Park, H.W.
Crystal structures of Klebsiella pneumoniae pantothenate kinase in complex with N-substituted pantothenamides.
Proteins, 81:1466-1472, 2013

PubMed Abstract: N-Substituted pantothenamides are derivatives of pantothenate, the precursor in the biosynthesis of the essential metabolic cofactor coenzyme A (CoA). These compounds are substrates of pantothenate kinase (PanK) in the first step of CoA biosynthesis and possess antimicrobial activity against various pathogenic bacteria. Here we solved the crystal structure of the Klebsiella pneumoniae PanK (KpPanK) in complex with N-pentylpantothenamide (N5-Pan) to understand the molecular basis of its antimicrobial activity. The structure reveals a polar pocket interacting with the pantothenate moiety of N5-Pan and an aromatic pocket loosely protecting the pentyl tail, suggesting that the introduction of an aromatic ring to a new pantothenamide may enhance the compound's affinity to KpPanK. To test this idea, we synthesized N-pyridin-3-ylmethylpantothenamide (Np-Pan) and solved its co-crystal structure with KpPanK. The structure reveals two alternat conformations of the aromatic ring of Np-Pan bound at the aromatic pocket, providing the basis for further improvement of pantothenamide binding to KpPanK.

PubMed: 23553820
DOI: 10.1002/prot.24290

実験手法

X-RAY DIFFRACTION (1.95 Å)