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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)6699-6702
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number21
DOIs
StatePublished - Jun 1 2016

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Nucleosomes
Methyltransferases
Methionine
Histones
Lysine
Enzymes
Substrates
Isotopes
Density functional theory
Cytoplasmic and Nuclear Receptors
Proteins
Multiple Myeloma
Neoplasms

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2. / Poulin, Myles B.; Schneck, Jessica L.; Matico, Rosalie E.; Hou, Wangfang; McDevitt, Patrick J.; Holbert, Marc; Schramm, Vern L.

In: Journal of the American Chemical Society, Vol. 138, No. 21, 01.06.2016, p. 6699-6702.

Research output: Contribution to journalArticle

Poulin, Myles B. ; Schneck, Jessica L. ; Matico, Rosalie E. ; Hou, Wangfang ; McDevitt, Patrick J. ; Holbert, Marc ; Schramm, Vern L. / Nucleosome binding alters the substrate bonding environment of histone H3 lysine 36 methyltransferase NSD2. In: Journal of the American Chemical Society. 2016 ; Vol. 138, No. 21. pp. 6699-6702.
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