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Information on EC 3.5.1.48 - acetylspermidine deacetylase and Organism(s) Danio rerio and UniProt Accession F1QCV2
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3.5.1.48 acetylspermidine deacetylaseIUBMB Comments
It was initially thought that N1-acetylspermidine was the substrate for this deacetylase reaction but this has since been disproved by Marchant et al. .
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Word Map
- 3.5.1.48
- deacetylases
-
deacetylation
-
hdac11
- mycoplana
- ramosa
- pharmacology
- drug development
The taxonomic range for the selected organisms is: Danio rerio
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
hdac10, histone deacetylase 10, acetylpolyamine amidohydrolase, polyamine deacetylase, n8-acetylspermidine deacetylase, zhdac10, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
N1-acetylspermidine amidohydrolase
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-
-
-
N8-acetyl-monoacetylspermidine deacetylase
-
-
-
-
N8-acetylspermidine deacetylase
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
N8-acetylspermidine amidohydrolase
It was initially thought that N1-acetylspermidine was the substrate for this deacetylase reaction [1] but this has since been disproved by Marchant et al. [3].
CAS REGISTRY NUMBER
COMMENTARY
67339-07-5
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin + H2O
?
very low activity
-
-
?
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin + H2O
?
very low activity
-
-
?
N-(3-aminopropyl)acetamide + H2O
propane-1,3-diamine + acetate
very low activity
-
-
?
N-(8-aminooctyl)acetamide + H2O
octane-1,8-diamine + acetate
moderate to high activity
-
-
?
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide + H2O
?
low activity
-
-
?
additional information
?
-
histone deacetylase 10 (HDAC10) from Danio rerio is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine
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-
?
additional information
?
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histone deacetylase 10 (HDAC10) from Danio rerio is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine
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-
?
additional information
?
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zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. The N4 amino group of N8-acetylspermidine is recognized by a direct hydrogen bond with E117. No activity with TK(ac)PIW, AK(ac)P, GAK(ac), AK(ac), AK(ac)A, K(ac)NL, K(ac)NL, and GAK(ac)NLQ
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-
?
additional information
?
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zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. The N4 amino group of N8-acetylspermidine is recognized by a direct hydrogen bond with E117. No activity with TK(ac)PIW, AK(ac)P, GAK(ac), AK(ac), AK(ac)A, K(ac)NL, K(ac)NL, and GAK(ac)NLQ
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
AAT, binds as a tetrahedral gem-diolate to both APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) and HDAC10, thereby mimicking the tetrahedral intermediate and its flanking transition states in catalysis
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
AAT, enzyme-bound structure analysis, overview. This inhibitor binds as a transition state analogue
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.017 - 0.07
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
0.066 - 0.15
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
0.08
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant wild-type enzyme
0.017
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.022
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.06
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.06
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.07
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.066
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.07
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.11
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.15
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.27
N8-Acetylspermidine
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00007 - 0.053
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
0.0013 - 0.21
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
0.013
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant wild-type enzyme
0.00007
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.00033
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.00046
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.021
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.053
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.0013
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.0013
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.0015
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.21
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.082
N8-Acetylspermidine
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
additional information
additional information
steady-state kinetics of wild-type and mutant enzymes
-
additional information
additional information
-
steady-state kinetics of wild-type and mutant enzymes
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0012 - 0.757
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
0.0087 - 8.84
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
0.163
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant wild-type enzyme
0.0012
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.015
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.027
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.35
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.757
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.0087
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.012
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.023
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
8.84
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.304
N8-Acetylspermidine
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0007
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
pH 8.0, 22°C, recombinant wild-type enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme adopts the characteristic arginase-deacetylase fold and employ a Zn2+-activated water molecule for catalysis. The active sites of HDAC10 and APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) are sterically constricted to enforce specificity for long, slender polyamine substrates and exclude bulky peptides and proteins containing acetyl-L-lysine. The tertiary structure (a unique 310 helix defined by the P(E,A)CE motif) provides the steric constriction that directs the polyamine substrate specificity of HDAC10. Structure and catalytic mechanism of polyamine deacetylases, comparison of HDAC and APAH, overview
physiological function
additional information
physiological function
Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation. Both HDAC10 and its product spermidine are known to promote cellular survival through autophagy
physiological function
HDAC10 and spermidine act as mediators of autophagy
additional information
nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview
additional information
-
nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HDA10_DANRE
675
0
74543
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme zHDAC10 mutant Y307F complexed with a polyamine transition state analogue inhibitor AAT, sitting drop vapour diffusion method, mixing of 400 nl of 30 mg/ml Y307F zHDAC10DELTA-AAT complex and 5 mM AAT with 400 nl of precipitant solution containing 0.2 M KH2PO4, and 20% PEG 3350, and equilibration against 0.08 ml precipitant solution, 24 h, 4°C, X-ray diffraction structure determination and analysis at 2.85 A resolution, molecular replacement using structure of the zHDAC6 CD1-TSA complex (PDB ID 5EEF)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E274L
site-directed mutagenesis, steady-state kinetics, mutation of the glutamate gatekeeper residue
Y307F
site-directed mutagenesis, introduction of the deactivating Y307F mutation facilitates crystallization
additional information
additional information
construction of deletion mutant DELTAnuA2, steady-state kinetics. The universal 310 helix nuA2 insertion in loop L1 further constricts the HDAC10 active site. Generation of mutant zHDAC10DELTA by treatement with trypsin
additional information
-
construction of deletion mutant DELTAnuA2, steady-state kinetics. The universal 310 helix nuA2 insertion in loop L1 further constricts the HDAC10 active site. Generation of mutant zHDAC10DELTA by treatement with trypsin
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant TEV-cleavable N-terminal His-MBP-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by amylose affinity chromatography, TEV protease is used to remove the His-MBP-tag, followed by anion exchange chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene hdac10, DNA and amino acid sequence determination and analysis, sequence comparisons, recombinant expression of TEV-cleavable N-terminal His-MBP-tagged enzyme from codon-optimized HDAC10 gene (residues 2-675) in Escherichia coli strain BL21(DE3), expression of wild-type and mutant enzymes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shinsky, S.A.; Christianson, D.W.
Polyamine deacetylase structure and catalysis prokaryotic acetylpolyamine amidohydrolase and eukaryotic HDAC10
Biochemistry
57
3105-3114
2018
Danio rerio (F1QCV2), Danio rerio, Homo sapiens (Q969S8), Homo sapiens
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