Structural basis for cytochrome c Y67H mutant to function as a peroxidase.

The catalytic activity of cytochrome c (cyt c) to peroxidize cardiolipin to its oxidized form is required for the release of pro-apoptotic factors from mitochondria, and for execution of the subsequent apoptotic steps. However, the structural basis for this peroxidation reaction remains unclear. In...

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Autores principales:	Wenxian Lan, Zhonghua Wang, Zhongzheng Yang, Tianlei Ying, Xu Zhang, Xiangshi Tan, Maili Liu, Chunyang Cao, Zhong-Xian Huang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d23331e85b8408fb13d1d4a9eb30d75
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spelling	oai:doaj.org-article:9d23331e85b8408fb13d1d4a9eb30d752021-11-25T06:01:02ZStructural basis for cytochrome c Y67H mutant to function as a peroxidase.1932-620310.1371/journal.pone.0107305https://doaj.org/article/9d23331e85b8408fb13d1d4a9eb30d752014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107305https://doaj.org/toc/1932-6203The catalytic activity of cytochrome c (cyt c) to peroxidize cardiolipin to its oxidized form is required for the release of pro-apoptotic factors from mitochondria, and for execution of the subsequent apoptotic steps. However, the structural basis for this peroxidation reaction remains unclear. In this paper, we determined the three-dimensional NMR solution structure of yeast cyt c Y67H variant with high peroxidase activity, which is almost similar to that of its native form. The structure reveals that the hydrogen bond between Met80 and residue 67 is disrupted. This change destabilizes the sixth coordination bond between heme Fe(3+) ion and Met80 sulfur atom in the Y67H variant, and further makes it more easily be broken at low pH conditions. The steady-state studies indicate that the Y67H variant has the highest peroxidase activities when pH condition is between 4.0 and 5.2. Finally, a mechanism is suggested for the peroxidation of cardiolipin catalyzed by the Y67H variant, where the residue His67 acts as a distal histidine, its protonation facilitates O-O bond cleavage of H2O2 by functioning as an acidic catalyst.Wenxian LanZhonghua WangZhongzheng YangTianlei YingXu ZhangXiangshi TanMaili LiuChunyang CaoZhong-Xian HuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107305 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenxian Lan Zhonghua Wang Zhongzheng Yang Tianlei Ying Xu Zhang Xiangshi Tan Maili Liu Chunyang Cao Zhong-Xian Huang Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
description	The catalytic activity of cytochrome c (cyt c) to peroxidize cardiolipin to its oxidized form is required for the release of pro-apoptotic factors from mitochondria, and for execution of the subsequent apoptotic steps. However, the structural basis for this peroxidation reaction remains unclear. In this paper, we determined the three-dimensional NMR solution structure of yeast cyt c Y67H variant with high peroxidase activity, which is almost similar to that of its native form. The structure reveals that the hydrogen bond between Met80 and residue 67 is disrupted. This change destabilizes the sixth coordination bond between heme Fe(3+) ion and Met80 sulfur atom in the Y67H variant, and further makes it more easily be broken at low pH conditions. The steady-state studies indicate that the Y67H variant has the highest peroxidase activities when pH condition is between 4.0 and 5.2. Finally, a mechanism is suggested for the peroxidation of cardiolipin catalyzed by the Y67H variant, where the residue His67 acts as a distal histidine, its protonation facilitates O-O bond cleavage of H2O2 by functioning as an acidic catalyst.
format	article
author	Wenxian Lan Zhonghua Wang Zhongzheng Yang Tianlei Ying Xu Zhang Xiangshi Tan Maili Liu Chunyang Cao Zhong-Xian Huang
author_facet	Wenxian Lan Zhonghua Wang Zhongzheng Yang Tianlei Ying Xu Zhang Xiangshi Tan Maili Liu Chunyang Cao Zhong-Xian Huang
author_sort	Wenxian Lan
title	Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
title_short	Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
title_full	Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
title_fullStr	Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
title_full_unstemmed	Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
title_sort	structural basis for cytochrome c y67h mutant to function as a peroxidase.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9d23331e85b8408fb13d1d4a9eb30d75
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Structural basis for cytochrome c Y67H mutant to function as a peroxidase.

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