7T1H

Crystal structure of CAB1 Pantothenate Kinase from Saccharomyces cerevisiae in complex with compound YU281445

7T1H の概要

• エントリーDOI: 10.2210/pdb7t1h/pdb
• 関連するPDBエントリー: 6UJ5 7T1G 7T1I
• 分子名称: Pantothenate kinase CAB1, (8R)-2-{[(4-tert-butylphenyl)methyl]amino}-5-[(morpholin-4-yl)methyl][1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Saccharomyces cerevisiae S288C
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84436.96

構造登録者

Gihaz, S.,Ben Mamoun, C. (登録日: 2021-12-01, 公開日: 2022-10-05, 最終更新日: 2023-10-18)

主引用文献

Gihaz, S.,Gareiss, P.,Choi, J.Y.,Renard, I.,Pal, A.C.,Surovsteva, Y.,Chiu, J.E.,Thekkiniath, J.,Plummer, M.,Hungerford, W.,Montgomery, M.L.,Hosford, A.,Adams, E.M.,Lightfoot, J.D.,Fox 3rd, D.,Ojo, K.K.,Staker, B.L.,Fuller, K.,Ben Mamoun, C.
High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development.
Structure, 30:1494-, 2022

PubMed Abstract: Fungal infections are the leading cause of mortality by eukaryotic pathogens, with an estimated 150 million severe life-threatening cases and 1.7 million deaths reported annually. The rapid emergence of multidrug-resistant fungal isolates highlights the urgent need for new drugs with new mechanisms of action. In fungi, pantothenate phosphorylation, catalyzed by PanK enzyme, is the first step in the utilization of pantothenic acid and coenzyme A biosynthesis. In all fungi sequenced so far, this enzyme is encoded by a single PanK gene. Here, we report the crystal structure of a fungal PanK alone as well as with high-affinity inhibitors from a single chemotype identified through a high-throughput chemical screen. Structural, biochemical, and functional analyses revealed mechanisms governing substrate and ligand binding, dimerization, and catalysis and helped identify new compounds that inhibit the growth of several Candida species. The data validate PanK as a promising target for antifungal drug development.

PubMed: 36167065
DOI: 10.1016/j.str.2022.09.001

実験手法

X-RAY DIFFRACTION (1.9 Å)