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Literature summary for 3.5.1.98 extracted from

  • Castaneda, C.A.; Lopez, J.E.; Joseph, C.G.; Scholle, M.D.; Mrksich, M.; Fierke, C.A.
    Active site metal identity alters histone deacetylase 8 substrate selectivity a potential novel regulatory mechanism (2017), Biochemistry, 56, 5663-5670 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.5.1.98

Inhibitors

Inhibitors Comment Organism Structure
suberoylanilide hydroxamic acid SAHA, Ki, for the T-cell lymphoma drug suberoylanilide hydroxamic acid (SAHA) is different for each metal-substituted HDAC8 Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Co2+ activates Homo sapiens
Fe2+ activates, Fe(II)-HDAC8 is sensitive to oxidation and is not activated by Fe(III) Homo sapiens
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 Homo sapiens
Zn2+ activates Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9BY41
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HeLa cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Boc-Lys(ac)-coumarin + H2O i.e. Boc-K(ac)-Fluor-de-Lys Homo sapiens Boc-Lys-coumarin + acetate
-
 ?
CKDLK(ac)RLFS + H2O i.e. CREB94 Homo sapiens CKDLKRLFS + acetate
-
 ?
LGDGK(ac)MKS + H2O i.e. THRAP3, low activity Homo sapiens LGDGKMKS + acetate
-
 ?
LGK(ac)FRR + H2O i.e. La-related protein 1, LARP1, best peptide substrate Homo sapiens LGKFRR + acetate
-
 ?
additional information 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, overview. Both protein structure and long-range HDAC8-substrate interactions contribute to substrate selectivity, peptide substrate evaluation Homo sapiens ?
-
-
RHK(ac)K(ac)-coumarin + H2O i.e. HDAC8 Fluor-de-Lys or HDAC8 p53 FdL, low activity Homo sapiens RHKK-coumarin + 2 acetate
-
 ?
RHKK(ac)-coumarin + H2O i.e. SIRT1 Fluor-de-Lys Homo sapiens RHKK-coumarin + acetate
-
 ?
RVIGAKK(ac)DQ + H2O a SMC3 9mer Homo sapiens RVIGAKKDQ + acetate
-
 ?
RVIGAKK(ac)DQY + H2O a SMC3 10mer Homo sapiens RVIGAKKDQY + acetate
-
 ?
STPVK(ac)FISR + H2O i.e. CSRP2BP Homo sapiens STPVKFISR + acetate
-
 ?
TKQTARK(ac)STGGKA + H2O a H3K9 13mer Homo sapiens TKQTARKSTGGKA + acetate
-
 ?

Synonyms

Synonyms Comment Organism
acetyl-lysine deacetylase
-
 Homo sapiens
class I acetyl-lysine deacetylase
-
 Homo sapiens
HDAC8
-
 Homo sapiens
histone deacetylase 8
-
 Homo sapiens

General Information

General Information Comment Organism
evolution histone deacetylase 8 (HDAC8) is a member of the class I acetyl-lysine deacetylase (HDAC) family Homo sapiens
physiological function the active site metal identity alters histone deacetylase 8 substrate selectivity, which may be a potential regulatory mechanism Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
additional information
-
 additional information substrate specifcity, catalytic efficiencies with different peptides substrates of the enzyme with bound Fe2+ and/or Zn2+, overview Homo sapiens