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Somoza, J.R., Skene, R.J., Katz, B.A., Mol, C., Ho, J.D., Jennings, A.J., Luong, C., Arvai, A., Buggy, J.J., Chi, E., Tang, J., Sang, B.C., Verner, E., Wynands, R., Leahy, E.M., Dougan, D.R., Snell, G., Navre, M., Knuth, M.W., Swanson, R.V., McRee, D.E. and Tari, L.W. (2004) Structural Snapshots of Human HDAC8 Provide Insights Into the Class I Histone Deacetylases. Structure (Cambridge), 12, 1325-1334.
https://doi.org/10.1016/j.str.2004.04.012

has been cited by the following article:

• TITLE: Biophysical Mechanism of the SAHA Inhibition of Zn2+-Histone Deacetylase-Like Protein (FB188 HDAH) Assessed via Crystal Structure Analysis

  AUTHORS: Cynthia Raquel Trejo-Muñoz, Ricardo Vázquez-Ramírez, Luis Mendoza, Carlos Kubli-Garfias

  KEYWORDS: SAHA, Deacetylase, FB188 HDAH, Free-Energy, Crystal-Analysis

  JOURNAL NAME: Computational Molecular Bioscience, Vol.8 No.2, June 28, 2018

  ABSTRACT: The zinc-containing enzyme HDAC-like amidohydrolase (FB188 HDAH), identified in the Bordetella alcaligenes bacteria, is similar to enzymes that participate in epigenetic mechanisms such as histone modifications. The X-ray crystal structure of FB188 HDAH complexed with the antagonist SAHA (suberoylanilide hydroxamic acid) has been solved (PDB ID: 1ZZ1). Notably, the complex crystallizes as a tetramer in the asymmetric unit cell of the crystal. The crystal yielded a suitable structure to analyze the dynamics of the inhibitory mechanism of SAHA on this histone deacetylase. Applying computational chemistry techniques and quantum mechanics theory, several physicochemical properties were calculated to compare the active site of the enzyme of the four monomers. Significant differences were observed in the areas and volumes of the binding pocket, as well as hydrophobic interactions, dipole moments, atomic charges and electrostatic potential, among other properties. Remarkably, a free-energy curve resulting from the evaluation of the energies of SAHA and the interacting amino acids of the four crystal monomers unveiled the biophysical mechanism of the FB188 HDAH inhibition exerted by SAHA to a greater extent. The biophysical mechanism of SAHA inhibition on FB188 deacetylase was clearly observed as a dynamic process. It is possible to define the physicochemical dynamics of the molecular complex by the application of computational chemistry techniques and quantum mechanics theory by studying the crystal structures of the interacting molecules.