Unexpected Deacetylation Mechanism Suggested by a Density Functional Theory QM/MM Study of Histone-Deacetylase-Like Protein

To characterize the catalytic mechanism for zinc-dependent histone deacetylases (HDAC), we have carried out d. functional theory (DFT) QM/MM studies on the deacetylation reaction catalyzed by a histone-deacetylase-like protein (HDLP). The calcn. 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. [on SciFinder (R)]


Published in:
Journal of the American Chemical Society, 128, 14, 4530-4531
Year:
2006
Keywords:
Note:
CAN 144:345770
7-4
Enzymes
Department of Chemistry,New York University,New York,NY,USA.
Journal
0002-7863
written in English.
7440-66-6 (Zinc); 9076-57-7 (Histone deacetylase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); 60-18-4 (L-Tyrosine); 71-00-1 (L-Histidine) Role: BSU (Biological study, unclassified), BIOL (Biological study) (catalytic role; DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein)
Laboratories:




 Record created 2007-10-22, last modified 2018-03-17


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