6NIV

Racemic Phenol-Soluble Modulin Alpha 3 Peptide

6NIV の概要

• エントリーDOI: 10.2210/pdb6niv/pdb
• 分子名称: Phenol-soluble modulin PSM-alpha-3 (2 entities in total)
• 機能のキーワード: peptide toxin, racemic crystallization, protein fibril
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2609.16

構造登録者

Yao, Z.,Cary, B.P.,Bingman, C.A.,Wang, C.,Kreitler, D.F.,Satyshur, K.A.,Forest, K.T.,Gellman, S.H. (登録日: 2018-12-31, 公開日: 2019-05-15, 最終更新日: 2024-11-13)

主引用文献

Yao, Z.,Cary, B.P.,Bingman, C.A.,Wang, C.,Kreitler, D.F.,Satyshur, K.A.,Forest, K.T.,Gellman, S.H.
Use of a Stereochemical Strategy To Probe the Mechanism of Phenol-Soluble Modulin alpha 3 Toxicity.
J.Am.Chem.Soc., 141:7660-7664, 2019

PubMed Abstract: Phenol-soluble modulin α3 (PSMα3) is a cytotoxic peptide secreted by virulent strains of Staphylococcus aureus. We used a stereochemical strategy to examine the mechanism of PSMα3-mediated toxicity. One hypothesis is that PSMα3 toxicity requires fibril formation; an alternative is that toxicity is caused by soluble forms of PSMα3, possibly oligomeric. We find that the unnatural enantiomer (D residues) displays cytotoxicity comparable to that of L-PSMα3. Racemic PSMα3 is similarly toxic to enantiopure PSMα3 (L or D) under some conditions, but the toxicity is lost under conditions that cause racemic PSMα3 to aggregate. A crystal structure of racemic PSMα3-NH displays an α-helical secondary structure and a packing pattern that is reminiscent of the cross-α arrangement recently discovered in crystals of L-PSMα3. Our data suggest that the cytotoxicity of PSMα3 does not depend on stereospecific engagement of a target protein or other chiral macromolecule, an observation that supports a mechanism based on membrane disruption. In addition, our data support the hypothesis that toxicity is exerted by a soluble form rather than an insoluble fibrillar form.

PubMed: 31045358
DOI: 10.1021/jacs.9b00349

実験手法

X-RAY DIFFRACTION (1.45 Å)