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

Autor: Mark E. Tuckerman, Po Hu, Clémence Corminboeuf, Yingkai Zhang
Rok vydání: 2006
Předmět:
Models
Molecular
Stereochemistry
Static Electricity
Protonation
unclassified)
Biochemistry
Histone Deacetylases
Catalysis
QM/MM
Colloid and Surface Chemistry
Static electricity
Histidine
histone deacetylase HDLP protein deacetylation mechanism calcn
biology
Chemistry
Water
Active site
Acetylation
Hydrogen Bonding
General Chemistry
Oxygen
Histone
biology.protein
Quantum Theory
Density functional theory
Histone deacetylase
BIOL (Biological study) (HDLP (histone-deacetylase-like protein)
DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein)
Enzyme functional sites (active
Complexation (zinc
Protonation (DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein)
Proteins Role: BSU (Biological study
Zdroj: Journal of the American Chemical Society. 128:4530-4531
ISSN: 1520-5126
0002-7863
Popis: 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)]
Databáze: OpenAIRE
Externí odkaz: