Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2

Myles B. Poulin; Jessica L. Schneck; Rosalie E. Matico; Wangfang Hou; Patrick J. McDevitt; Marc Holbert; Vern L. Schramm

doi:10.1021/jacs.6b01612

Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2

Myles B. Poulin, Jessica L. Schneck, Rosalie E. Matico, Wangfang Hou, Patrick J. McDevitt, Marc Holbert, Vern L. Schramm

Biochemistry

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone H3 lysine 36 (H3K36)-specific methyltransferase enzyme that is overexpressed in a number of cancers, including multiple myeloma. NSD2 binds to S-adenosyl-l-methionine (SAM) and nucleosome substrates to catalyze the transfer of a methyl group from SAM to the ϵ-amino group of histone H3K36. Equilibrium binding isotope effects and density functional theory calculations indicate that the SAM methyl group is sterically constrained in complex with NSD2, and that this steric constraint is released upon nucleosome binding. Together, these results show that nucleosome binding to NSD2 induces a significant change in the chemical environment of enzyme-bound SAM.

Original language	English (US)
Pages (from-to)	6699-6702
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	138
Issue number	21
DOIs	https://doi.org/10.1021/jacs.6b01612
State	Published - Jun 1 2016

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/jacs.6b01612

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title = "Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2",

abstract = "Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone H3 lysine 36 (H3K36)-specific methyltransferase enzyme that is overexpressed in a number of cancers, including multiple myeloma. NSD2 binds to S-adenosyl-l-methionine (SAM) and nucleosome substrates to catalyze the transfer of a methyl group from SAM to the ϵ-amino group of histone H3K36. Equilibrium binding isotope effects and density functional theory calculations indicate that the SAM methyl group is sterically constrained in complex with NSD2, and that this steric constraint is released upon nucleosome binding. Together, these results show that nucleosome binding to NSD2 induces a significant change in the chemical environment of enzyme-bound SAM.",

author = "Poulin, {Myles B.} and Schneck, {Jessica L.} and Matico, {Rosalie E.} and Wangfang Hou and McDevitt, {Patrick J.} and Marc Holbert and Schramm, {Vern L.}",

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T1 - Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2

AU - Poulin, Myles B.

AU - Schneck, Jessica L.

AU - Matico, Rosalie E.

AU - Hou, Wangfang

AU - McDevitt, Patrick J.

AU - Holbert, Marc

AU - Schramm, Vern L.

PY - 2016/6/1

Y1 - 2016/6/1

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AB - Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone H3 lysine 36 (H3K36)-specific methyltransferase enzyme that is overexpressed in a number of cancers, including multiple myeloma. NSD2 binds to S-adenosyl-l-methionine (SAM) and nucleosome substrates to catalyze the transfer of a methyl group from SAM to the ϵ-amino group of histone H3K36. Equilibrium binding isotope effects and density functional theory calculations indicate that the SAM methyl group is sterically constrained in complex with NSD2, and that this steric constraint is released upon nucleosome binding. Together, these results show that nucleosome binding to NSD2 induces a significant change in the chemical environment of enzyme-bound SAM.

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Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2

Abstract

ASJC Scopus subject areas

UN SDGs

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