Unexpected deacetylation mechanism suggested by a density functional theory QM/MM study of histone-deacetylase-like protein

Clémence Corminboeuf, Po Hu, Mark Tuckerman, Yingkai Zhang

Research output: Contribution to journalArticle

Abstract

To characterize the catalytic mechanism for zinc-dependent histone deacetylases (HDAC), we have carried out density functional theory QM/MM studies on the deacetylation reaction catalyzed by a histone-deacetylase-like protein (HDLP). The calculation results do not support the previous mechanistic hypothesis, but suggest a lower protonation state for the active site as well as a 4-fold zinc coordination during the reaction process. To characterize such mechanistic difference is not only significant for our fundamental understanding of its inner workings but also crucial for the design of HDAC inhibitors.

Original languageEnglish (US)
Pages (from-to)4530-4531
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number14
DOIs
StatePublished - Apr 12 2006

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Histone Deacetylases
Density functional theory
Proteins
Zinc
Protonation
Catalytic Domain

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Unexpected deacetylation mechanism suggested by a density functional theory QM/MM study of histone-deacetylase-like protein. / Corminboeuf, Clémence; Hu, Po; Tuckerman, Mark; Zhang, Yingkai.

In: Journal of the American Chemical Society, Vol. 128, No. 14, 12.04.2006, p. 4530-4531.

Research output: Contribution to journalArticle

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