Modeling a new water channel that allows SET9 to dimethylate p53.

SET9, a protein lysine methyltransferase, has been thought to be capable of transferring only one methyl group to target lysine residues. However, some reports have pointed out that SET9 can dimethylate Lys372 of p53 (p53-K372) and Lys4 of histone H3 (H3-K4). In order to understand how p53 can be di...

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Autores principales:	Qifeng Bai, Yulin Shen, Xiaojun Yao, Fang Wang, Yuping Du, Qin Wang, Nengzhi Jin, Jun Hai, Tiejun Hu, Jinbo Yang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41031eef543b47d1b0fbab36ede7399d
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spelling	oai:doaj.org-article:41031eef543b47d1b0fbab36ede7399d2021-11-18T06:53:39ZModeling a new water channel that allows SET9 to dimethylate p53.1932-620310.1371/journal.pone.0019856https://doaj.org/article/41031eef543b47d1b0fbab36ede7399d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625555/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203SET9, a protein lysine methyltransferase, has been thought to be capable of transferring only one methyl group to target lysine residues. However, some reports have pointed out that SET9 can dimethylate Lys372 of p53 (p53-K372) and Lys4 of histone H3 (H3-K4). In order to understand how p53 can be dimethylated by SET9, we measured the radius of the channel that surrounds p53-K372, first on the basis of the crystal structure of SET9, and we show that the channel is not suitable for water movement. Second, molecular dynamic (MD) simulations were carried out for 204 ns on the crystal structure of SET9. The results show that water leaves the active site of SET9 through a new channel, which is made of G292, A295, Y305 and Y335. In addition, the results of molecular docking and MD simulations indicate that the new water channel continues to remain open when S-adenosyl-L-methionine (AdoMet) or S-adenosyl-L-homocysteine (AdoHcy) is bound to SET9. The changes in the radii of these two channels were measured in the equilibrium phase at the constant temperature of 300 K. The results indicate that the first channel still does not allow water to get into or out of the active site, but the new channel is large enough to allow this water to circulate. Our results indicate that water can be removed from the active site, an essential process for allowing the dimethylation reaction to occur.Qifeng BaiYulin ShenXiaojun YaoFang WangYuping DuQin WangNengzhi JinJun HaiTiejun HuJinbo YangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19856 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qifeng Bai Yulin Shen Xiaojun Yao Fang Wang Yuping Du Qin Wang Nengzhi Jin Jun Hai Tiejun Hu Jinbo Yang Modeling a new water channel that allows SET9 to dimethylate p53.
description	SET9, a protein lysine methyltransferase, has been thought to be capable of transferring only one methyl group to target lysine residues. However, some reports have pointed out that SET9 can dimethylate Lys372 of p53 (p53-K372) and Lys4 of histone H3 (H3-K4). In order to understand how p53 can be dimethylated by SET9, we measured the radius of the channel that surrounds p53-K372, first on the basis of the crystal structure of SET9, and we show that the channel is not suitable for water movement. Second, molecular dynamic (MD) simulations were carried out for 204 ns on the crystal structure of SET9. The results show that water leaves the active site of SET9 through a new channel, which is made of G292, A295, Y305 and Y335. In addition, the results of molecular docking and MD simulations indicate that the new water channel continues to remain open when S-adenosyl-L-methionine (AdoMet) or S-adenosyl-L-homocysteine (AdoHcy) is bound to SET9. The changes in the radii of these two channels were measured in the equilibrium phase at the constant temperature of 300 K. The results indicate that the first channel still does not allow water to get into or out of the active site, but the new channel is large enough to allow this water to circulate. Our results indicate that water can be removed from the active site, an essential process for allowing the dimethylation reaction to occur.
format	article
author	Qifeng Bai Yulin Shen Xiaojun Yao Fang Wang Yuping Du Qin Wang Nengzhi Jin Jun Hai Tiejun Hu Jinbo Yang
author_facet	Qifeng Bai Yulin Shen Xiaojun Yao Fang Wang Yuping Du Qin Wang Nengzhi Jin Jun Hai Tiejun Hu Jinbo Yang
author_sort	Qifeng Bai
title	Modeling a new water channel that allows SET9 to dimethylate p53.
title_short	Modeling a new water channel that allows SET9 to dimethylate p53.
title_full	Modeling a new water channel that allows SET9 to dimethylate p53.
title_fullStr	Modeling a new water channel that allows SET9 to dimethylate p53.
title_full_unstemmed	Modeling a new water channel that allows SET9 to dimethylate p53.
title_sort	modeling a new water channel that allows set9 to dimethylate p53.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/41031eef543b47d1b0fbab36ede7399d
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_version_	1718424223779651584

Modeling a new water channel that allows SET9 to dimethylate p53.

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