3.5.1.98	Co2+	-	696240	
3.5.1.98	Co2+	activates	756047	
3.5.1.98	Co2+	ratio of kcat to KM value in presence of metal ion in decreasing order: Co(II), Fe(II), Zn(II), Ni(II)	678192	
3.5.1.98	Fe2+	-	696240	
3.5.1.98	Fe2+	activates, Fe(II)-HDAC8 is sensitive to oxidation and is not activated by Fe(III)	756047	
3.5.1.98	Fe2+	isozyme HDAC8 has higher activity with a bound Fe(II) than Zn(II), although Fe(II)-HDAC8 rapidly loses activity under aerobic conditions	735224	
3.5.1.98	Fe2+	ratio of kcat to KM value in presence of metal ion in decreasing order: Co(II), Fe(II), Zn(II), Ni(II). Fe(II) bound to enzyme is readily oxidized to Fe(III) upon exposure to oxygen	678192	
3.5.1.98	K+	K+ bound to monovalent cation site 2 enhances catalytic activity of HDAC8 45fold with maximal deacetylase activity observed at 10 mM KCl. K+ is the predominant monovalent cation bound to HDAC8 in vivo, K+ binding to site 1 enhances the affinity of HDAC8 for suberoylanilide hydroxamic acid	712485	
3.5.1.98	K+	presence of two potassium ions in the structure of isoform HDAC8, one of which interacts with the key catalytic residues. Direct role of potassium in fold stabilization	682501	
3.5.1.98	Mg2+	required	733817	
3.5.1.98	Mg2+	Zn2+, Mg2+, or Mn2+ is required. Zn2+ is the most efficient	677978	
3.5.1.98	Mn2+	Zn2+, Mg2+, or Mn2+ is required. Zn2+ is the most efficient	677978	
3.5.1.98	additional information	the active site metal identity alters histone deacetylase 8 substrate selectivity. HDAC8 is activated by several divalent metal ions suggesting metal-dependent regulation of this enzyme in vivo. Fe(II)-HDAC8 catalyzes deacetylation of peptides comparable to or faster than Zn(II)-HDAC8. The residues that coordinate the active site metal ion (His180, Asp267, and Asp178) are positioned by the flexible loops. Intrinsic properties of the metal ion, including Lewis acidity and size, can influence the structure and dynamics of the loop regions and alter the binding interface presented to substrates. Altering the active site metal ion coordination is expected to propagate structural changes to the peptide binding site via the residues in the hydrophobic shell around the metal ligands	756047	
3.5.1.98	additional information	the identity of the catalytic metal ion influences both the Michaelis-Menten constant and the affinity of inhibitor suberoylanilide hydroxamic acid, with Fe(II) and Co(II) giving KM values 5fold lower than that of Zn(II). Apo-enzyme has a low residual level of activity	678192	
3.5.1.98	Na+	Na+ binds more weakly to both monovalent cation sites and activates HDAC8 to a lesser extent than K+	712485	
3.5.1.98	Ni2+	ratio of kcat to KM value in presence of metal ion in decreasing order: Co(II), Fe(II), Zn(II), Ni(II)	678192	
3.5.1.98	Zinc	enzyme active site consists of a tubular pocket, a zinc-binding site and two D-H charge-relay systems	682087	
3.5.1.98	Zn2+	-	696240, 696610, 696616, 697087, 697650, 698491, 698743, 699231, 699429, 699458, 700547	
3.5.1.98	Zn2+	activates	756047	
3.5.1.98	Zn2+	bound in the catalytic pocket	756174	
3.5.1.98	Zn2+	ratio of kcat to KM value in presence of metal ion in decreasing order: Co(II), Fe(II), Zn(II), Ni(II)	678192	
3.5.1.98	Zn2+	required for activity	756043	
3.5.1.98	Zn2+	required, enzyme bound	735331	
3.5.1.98	Zn2+	zinc-dependent	756690	
3.5.1.98	Zn2+	zinc-dependent enzyme	733951	
3.5.1.98	Zn2+	Zn(II)-dependent deacetylase, but isozyme HDAC8 has higher activity with a bound Fe(II) than Zn(II), although Fe(II)-HDAC8 rapidly loses activity under aerobic conditions	735224	
3.5.1.98	Zn2+	Zn2+, Mg2+, or Mn2+ is required. Zn2+ is the most efficient	677978