2K0N

Solution Structure of Yeast Gal11p kix domain

2K0N の概要

• エントリーDOI: 10.2210/pdb2k0n/pdb
• 分子名称: Mediator of RNA polymerase II transcription subunit 15 (1 entity in total)
• 機能のキーワード: protein, activator, nucleus, phosphoprotein, transcription, transcription regulation
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Nucleus: P19659
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9408.61

構造登録者

Arthanari, H.,Frueh, D.P.,Wagner, G.K.,Naar, A.M. (登録日: 2008-02-04, 公開日: 2008-03-25, 最終更新日: 2024-05-29)

主引用文献

Thakur, J.K.,Arthanari, H.,Yang, F.,Pan, S.J.,Fan, X.,Breger, J.,Frueh, D.P.,Gulshan, K.,Li, D.K.,Mylonakis, E.,Struhl, K.,Moye-Rowley, W.S.,Cormack, B.P.,Wagner, G.,Naar, A.M.
A nuclear receptor-like pathway regulating multidrug resistance in fungi.
Nature, 452:604-609, 2008

PubMed Abstract: Multidrug resistance (MDR) is a serious complication during treatment of opportunistic fungal infections that frequently afflict immunocompromised individuals, such as transplant recipients and cancer patients undergoing cytotoxic chemotherapy. Improved knowledge of the molecular pathways controlling MDR in pathogenic fungi should facilitate the development of novel therapies to combat these intransigent infections. MDR is often caused by upregulation of drug efflux pumps by members of the fungal zinc-cluster transcription-factor family (for example Pdr1p orthologues). However, the molecular mechanisms are poorly understood. Here we show that Pdr1p family members in Saccharomyces cerevisiae and the human pathogen Candida glabrata directly bind to structurally diverse drugs and xenobiotics, resulting in stimulated expression of drug efflux pumps and induction of MDR. Notably, this is mechanistically similar to regulation of MDR in vertebrates by the PXR nuclear receptor, revealing an unexpected functional analogy of fungal and metazoan regulators of MDR. We have also uncovered a critical and specific role of the Gal11p/MED15 subunit of the Mediator co-activator and its activator-targeted KIX domain in antifungal/xenobiotic-dependent regulation of MDR. This detailed mechanistic understanding of a fungal nuclear receptor-like gene regulatory pathway provides novel therapeutic targets for the treatment of multidrug-resistant fungal infections.

PubMed: 18385733
DOI: 10.1038/nature06836

実験手法

SOLUTION NMR