3W7F

Crystal structure of the C(30) carotenoid dehydrosqualene synthase from staphylococcus aureus complexed with farnesyl thiopyrophosphate

「2ZCP」から置き換えられました

3W7F の概要

• エントリーDOI: 10.2210/pdb3w7f/pdb
• 関連するPDBエントリー: 2ZCO
• 分子名称: Dehydrosqualene synthase, S-[(2E,6E)-3,7,11-TRIMETHYLDODECA-2,6,10-TRIENYL] TRIHYDROGEN THIODIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: crtm, fspp, carotenoid biosynthesis, staphyloxanthin biosynthesis, transferase, head-to-head condensation
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71314.39

構造登録者

Liu, C.I.,Jeng, W.Y.,Wang, A.H.,Oldfield, E. (登録日: 2013-02-28, 公開日: 2013-04-10, 最終更新日: 2023-11-08)

主引用文献

Liu, C.I.,Liu, G.Y.,Song, Y.,Yin, F.,Hensler, M.E.,Jeng, W.Y.,Nizet, V.,Wang, A.H.,Oldfield, E.
A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence.
Science, 319:1391-1394, 2008

PubMed Abstract: Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration approximately 100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor-based therapy against S. aureus.

PubMed: 18276850
DOI: 10.1126/science.1153018

実験手法

X-RAY DIFFRACTION (2.25 Å)