A comparative molecular dynamics study of methylation state specificity of JMJD2A.

Histone modifications have great importance in epigenetic regulation. JMJD2A is a histone demethylase which is selective for di- and trimethyl forms of residues Lys9 and Lys36 of Histone 3 tail (H3K9 and H3K36). We present a molecular dynamics simulations of mono-, di- and trimethylated histone tail...

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Autores principales:	Ozlem Ulucan, Ozlem Keskin, Burak Erman, Attila Gursoy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dee6f486f34b4a0fa70c73da106466a3
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spelling	oai:doaj.org-article:dee6f486f34b4a0fa70c73da106466a32021-11-04T06:08:43ZA comparative molecular dynamics study of methylation state specificity of JMJD2A.1932-620310.1371/journal.pone.0024664https://doaj.org/article/dee6f486f34b4a0fa70c73da106466a32011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931800/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Histone modifications have great importance in epigenetic regulation. JMJD2A is a histone demethylase which is selective for di- and trimethyl forms of residues Lys9 and Lys36 of Histone 3 tail (H3K9 and H3K36). We present a molecular dynamics simulations of mono-, di- and trimethylated histone tails in complex with JMJD2A catalytic domain to gain insight into how JMJD2A discriminates between the methylation states of H3K9. The methyl groups are located at specific distances and orientations with respect to Fe(II) in methylammonium binding pocket. For the trimethyllysine the mechanism which provides the effectual orientation of methyl groups is the symmetry, whereas for the dimethyllysine case the determining factors are the interactions between methyllysine head and its environment and subsequently the restriction on angular motion. The occurrence frequency of methyl groups in a certain proximity of Fe(II) comes out as the explanation of the enzyme activity difference on di- and tri-methylated peptides. Energy analysis suggests that recognition is mostly driven by van der Waals and followed by Coulombic interactions in the enzyme-substrate interface. The number (mono, di or tri) and orientations of methyl groups and water molecules significantly affect the extent of van der Waals interaction strengths. Hydrogen bonding analysis suggests that the interaction between JMJD2A and its substrates mainly comes from main chain-side chain interactions. Binding free energy analysis points out Arg8 as an important residue forming an intra-substrate hydrogen bond with tri and dimethylated Lys9 of the H3 chain. Our study provides new insights into how JMJD2A discriminates between its substrates from both a structural and dynamical point of view.Ozlem UlucanOzlem KeskinBurak ErmanAttila GursoyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24664 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ozlem Ulucan Ozlem Keskin Burak Erman Attila Gursoy A comparative molecular dynamics study of methylation state specificity of JMJD2A.
description	Histone modifications have great importance in epigenetic regulation. JMJD2A is a histone demethylase which is selective for di- and trimethyl forms of residues Lys9 and Lys36 of Histone 3 tail (H3K9 and H3K36). We present a molecular dynamics simulations of mono-, di- and trimethylated histone tails in complex with JMJD2A catalytic domain to gain insight into how JMJD2A discriminates between the methylation states of H3K9. The methyl groups are located at specific distances and orientations with respect to Fe(II) in methylammonium binding pocket. For the trimethyllysine the mechanism which provides the effectual orientation of methyl groups is the symmetry, whereas for the dimethyllysine case the determining factors are the interactions between methyllysine head and its environment and subsequently the restriction on angular motion. The occurrence frequency of methyl groups in a certain proximity of Fe(II) comes out as the explanation of the enzyme activity difference on di- and tri-methylated peptides. Energy analysis suggests that recognition is mostly driven by van der Waals and followed by Coulombic interactions in the enzyme-substrate interface. The number (mono, di or tri) and orientations of methyl groups and water molecules significantly affect the extent of van der Waals interaction strengths. Hydrogen bonding analysis suggests that the interaction between JMJD2A and its substrates mainly comes from main chain-side chain interactions. Binding free energy analysis points out Arg8 as an important residue forming an intra-substrate hydrogen bond with tri and dimethylated Lys9 of the H3 chain. Our study provides new insights into how JMJD2A discriminates between its substrates from both a structural and dynamical point of view.
format	article
author	Ozlem Ulucan Ozlem Keskin Burak Erman Attila Gursoy
author_facet	Ozlem Ulucan Ozlem Keskin Burak Erman Attila Gursoy
author_sort	Ozlem Ulucan
title	A comparative molecular dynamics study of methylation state specificity of JMJD2A.
title_short	A comparative molecular dynamics study of methylation state specificity of JMJD2A.
title_full	A comparative molecular dynamics study of methylation state specificity of JMJD2A.
title_fullStr	A comparative molecular dynamics study of methylation state specificity of JMJD2A.
title_full_unstemmed	A comparative molecular dynamics study of methylation state specificity of JMJD2A.
title_sort	comparative molecular dynamics study of methylation state specificity of jmjd2a.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/dee6f486f34b4a0fa70c73da106466a3
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A comparative molecular dynamics study of methylation state specificity of JMJD2A.

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