PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 28937750-0 2017 Active Site Metal Identity Alters Histone Deacetylase 8 Substrate Selectivity: A Potential Novel Regulatory Mechanism. Metals 12-17 histone deacetylase 8 Homo sapiens 34-55 20568751-0 2010 A proton-shuttle reaction mechanism for histone deacetylase 8 and the catalytic role of metal ions. Metals 88-93 histone deacetylase 8 Homo sapiens 40-61 31633931-6 2019 However, the magnitude of the effect depends on the peptide sequence and the identity of the active site metal ion [Zn(II) vs Fe(II)], with the value of kcat/KM for the mutant decreasing 9- to >200-fold compared to that of wild-type HDAC8. Metals 105-110 histone deacetylase 8 Homo sapiens 233-238 20545365-0 2010 Structures of metal-substituted human histone deacetylase 8 provide mechanistic inferences on biological function . Metals 14-19 histone deacetylase 8 Homo sapiens 38-59 16681389-0 2006 Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion. Metals 113-118 histone deacetylase 8 Homo sapiens 43-64 16681389-4 2006 Here we demonstrate that histone deacetylase 8 (HDAC8) is catalytically active with a number of divalent metal ions in a 1:1 stoichiometry with the following order of specific activity: Co(II) > Fe(II) > Zn(II) > Ni(II). Metals 105-110 histone deacetylase 8 Homo sapiens 25-46 16681389-4 2006 Here we demonstrate that histone deacetylase 8 (HDAC8) is catalytically active with a number of divalent metal ions in a 1:1 stoichiometry with the following order of specific activity: Co(II) > Fe(II) > Zn(II) > Ni(II). Metals 105-110 histone deacetylase 8 Homo sapiens 48-53 16681389-5 2006 The identity of the catalytic metal ion influences both the affinity of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the Michaelis constant, with Fe(II)- and Co(II)-HDAC8 having K(M) values that are over 5-fold lower than that of Zn(II)-HDAC8. Metals 30-35 histone deacetylase 8 Homo sapiens 247-259 16681389-8 2006 Identification of the in vivo metal ion of HDAC8 is essential for understanding the biological function and regulation of HDAC8 and for the development of improved inhibitors of this class of enzymes. Metals 30-35 histone deacetylase 8 Homo sapiens 43-48 16681389-8 2006 Identification of the in vivo metal ion of HDAC8 is essential for understanding the biological function and regulation of HDAC8 and for the development of improved inhibitors of this class of enzymes. Metals 30-35 histone deacetylase 8 Homo sapiens 122-127 28937750-2 2017 Previous work has shown that the efficiency of HDAC8-catalyzed deacetylation of a methylcoumarin peptide varies depending on the identity of the divalent metal ion in the HDAC8 active site. Metals 154-159 histone deacetylase 8 Homo sapiens 47-52 28937750-2 2017 Previous work has shown that the efficiency of HDAC8-catalyzed deacetylation of a methylcoumarin peptide varies depending on the identity of the divalent metal ion in the HDAC8 active site. Metals 154-159 histone deacetylase 8 Homo sapiens 171-176 28937750-3 2017 Here we demonstrate that both HDAC8 activity and substrate selectivity for a diverse range of peptide substrates depend on the identity of the active site metal ion. Metals 155-160 histone deacetylase 8 Homo sapiens 30-35 28937750-7 2017 These data provide support for the hypothesis that HDAC8 may undergo metal switching in vivo that, in turn, may regulate its activity. Metals 69-74 histone deacetylase 8 Homo sapiens 51-56 28937750-8 2017 However, future studies are needed to explore the identity of the metal ion bound to HDAC8 in cells under varied conditions. Metals 66-71 histone deacetylase 8 Homo sapiens 85-90 27774878-1 2017 BACKGROUND: Histone deacetylase 8 (HDAC8) is a plausible target for the development of novel anticancer drugs using a metal-chelating group and hydrophobic moieties as pharmacophores. Metals 118-123 histone deacetylase 8 Homo sapiens 12-33 27774878-1 2017 BACKGROUND: Histone deacetylase 8 (HDAC8) is a plausible target for the development of novel anticancer drugs using a metal-chelating group and hydrophobic moieties as pharmacophores. Metals 118-123 histone deacetylase 8 Homo sapiens 35-40 25516458-0 2015 Kinetics and thermodynamics of metal-binding to histone deacetylase 8. Metals 31-36 histone deacetylase 8 Homo sapiens 48-69 25516458-6 2015 fl-SAHA binds specifically to metal-bound HDAC8 with affinities comparable to SAHA. Metals 30-35 histone deacetylase 8 Homo sapiens 42-47 25516458-8 2015 The metal KD values for HDAC8 are significantly different, ranging from picomolar to micromolar for Zn(II) and Fe(II), respectively. Metals 4-9 histone deacetylase 8 Homo sapiens 24-29 25516458-10 2015 Furthermore, monovalent cations (K(+) or Na(+)) that bind to HDAC8 decrease the dissociation rate constant of Zn(II) by >=100-fold for K(+) and >=10-fold for Na(+), suggesting a possible mechanism for regulating metal exchange in vivo. Metals 218-223 histone deacetylase 8 Homo sapiens 61-66 25516458-11 2015 The HDAC8 metal affinities are comparable to the readily exchangeable Zn(II) and Fe(II) concentrations in cells, consistent with either or both metal cofactors activating HDAC8. Metals 10-15 histone deacetylase 8 Homo sapiens 4-9 25516458-11 2015 The HDAC8 metal affinities are comparable to the readily exchangeable Zn(II) and Fe(II) concentrations in cells, consistent with either or both metal cofactors activating HDAC8. Metals 144-149 histone deacetylase 8 Homo sapiens 4-9 25516458-11 2015 The HDAC8 metal affinities are comparable to the readily exchangeable Zn(II) and Fe(II) concentrations in cells, consistent with either or both metal cofactors activating HDAC8. Metals 144-149 histone deacetylase 8 Homo sapiens 171-176 27933794-1 2016 Histone deacetylase 8 (HDAC8) catalyzes the hydrolysis of acetyl-l-lysine to yield products l-lysine and acetate through a mechanism in which a nucleophilic water molecule is activated by a histidine general base and a catalytic metal ion (Zn2+ or Fe2+). Metals 229-234 histone deacetylase 8 Homo sapiens 0-21 27933794-1 2016 Histone deacetylase 8 (HDAC8) catalyzes the hydrolysis of acetyl-l-lysine to yield products l-lysine and acetate through a mechanism in which a nucleophilic water molecule is activated by a histidine general base and a catalytic metal ion (Zn2+ or Fe2+). Metals 229-234 histone deacetylase 8 Homo sapiens 23-28 26996235-0 2016 Histone Deacetylase 8: Characterization of Physiological Divalent Metal Catalysis. Metals 66-71 histone deacetylase 8 Homo sapiens 0-21 26996235-12 2016 We use the quantum theory of atoms in molecules (QTAIM) to understand the different binding affinities for each metal in HDAC8 as well as the ability of each metal to bind and properly orient the substrate for deacetylation. Metals 112-117 histone deacetylase 8 Homo sapiens 121-126 26806311-2 2016 HDAC8 is a metal-dependent class I HDAC and is proposed to use a general acid-base catalytic pair in the mechanism of amide bond hydrolysis. Metals 11-16 histone deacetylase 8 Homo sapiens 0-5 26806311-8 2016 The upper pKa reflects the ionization of the metal-bound water molecule and shifts to 9.1 in Zn(II)-HDAC8. Metals 45-50 histone deacetylase 8 Homo sapiens 100-105