APAH_MYCRA
ID APAH_MYCRA Reviewed; 341 AA.
AC Q48935;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Acetylpolyamine amidohydrolase {ECO:0000303|PubMed:3207420, ECO:0000303|PubMed:8824626};
DE Short=APAH {ECO:0000303|PubMed:21268586};
DE EC=3.5.1.- {ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
DE AltName: Full=Acetylcadaverine deacetylase {ECO:0000305|PubMed:3207420};
DE AltName: Full=Acetylpolyamine deacetylase {ECO:0000305};
DE AltName: Full=Acetylputrescine deacetylase {ECO:0000305|PubMed:3207420};
DE EC=3.5.1.62 {ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
DE AltName: Full=Acetylspermidine deacetylase {ECO:0000305|PubMed:3207420};
DE EC=3.5.1.48 {ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
GN Name=aphA {ECO:0000303|PubMed:8824626}; Synonyms=aph;
OS Mycoplana ramosa (Mycoplana bullata).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Brucellaceae; Mycoplana.
OX NCBI_TaxID=40837;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-30, FUNCTION,
RP CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP COFACTOR, ACTIVITY REGULATION, AND PATHWAY.
RC STRAIN=ATCC 49678 / DSM 7292 / JCM 7822 / NBRC 15249 / NCIMB 9440 / FERM
RC BP-1845;
RX PubMed=8824626; DOI=10.1128/jb.178.19.5781-5786.1996;
RA Sakurada K., Ohta T., Fujishiro K., Hasegawa M., Aisaka K.;
RT "Acetylpolyamine amidohydrolase from Mycoplana ramosa: gene cloning and
RT characterization of the metal-substituted enzyme.";
RL J. Bacteriol. 178:5781-5786(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, COFACTOR, SUBUNIT,
RP ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 49678 / DSM 7292 / JCM 7822 / NBRC 15249 / NCIMB 9440 / FERM
RC BP-1845;
RX PubMed=3207420; DOI=10.1016/s0006-291x(88)80997-5;
RA Fujishiro K., Ando M., Uwajima T.;
RT "Crystallization and some properties of acetylpolyamine amidohydrolase from
RT Mycoplana bullata.";
RL Biochem. Biophys. Res. Commun. 157:1169-1174(1988).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-59 IN
RP COMPLEXES WITH ZINC; N8-ACETYLSPERMIDINE AND ACETYLSPERMINE SUBSTRATES; A
RP TRANSITION STATE ANALOG AND A HYDROXAMATE INHIBITOR, FUNCTION, SUBUNIT,
RP COFACTOR, ACTIVITY REGULATION, ACTIVE SITE, AND MUTAGENESIS OF HIS-158;
RP HIS-159 AND TYR-323.
RC STRAIN=ATCC 49678 / DSM 7292 / JCM 7822 / NBRC 15249 / NCIMB 9440 / FERM
RC BP-1845;
RX PubMed=21268586; DOI=10.1021/bi101859k;
RA Lombardi P.M., Angell H.D., Whittington D.A., Flynn E.F., Rajashankar K.R.,
RA Christianson D.W.;
RT "Structure of prokaryotic polyamine deacetylase reveals evolutionary
RT functional relationships with eukaryotic histone deacetylases.";
RL Biochemistry 50:1808-1817(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.13 ANGSTROMS) IN COMPLEXES WITH ZINC IONS AND
RP SEVERAL SUBSTRATE ANALOG INHIBITORS, ACTIVITY REGULATION, COFACTOR,
RP REACTION MECHANISM, AND ACTIVE SITE.
RX PubMed=26200446; DOI=10.1021/acs.biochem.5b00536;
RA Decroos C., Christianson D.W.;
RT "Design, synthesis, and evaluation of polyamine deacetylase inhibitors, and
RT high-resolution crystal structures of their complexes with acetylpolyamine
RT amidohydrolase.";
RL Biochemistry 54:4692-4703(2015).
CC -!- FUNCTION: Involved in polyamine metabolism. Catalyzes the deacetylation
CC of various acetylated polyamines such as N-acetylputrescine, N-
CC acetylcadaverine, N(1)-acetylspermine, N(1)-acetylspermidine and N(8)-
CC acetylspermidine (PubMed:8824626, PubMed:3207420). In vitro, is also
CC able to deacetylate L-Lys(epsilon-acetyl)coumarin, but has very low
CC activity towards the larger tetrapeptide N-acetyl-L-Arg-L-His-L-
CC Lys(epsilon-acetyl)-L-Lys(epsilon-acetyl)coumarin (PubMed:21268586).
CC {ECO:0000269|PubMed:21268586, ECO:0000269|PubMed:3207420,
CC ECO:0000269|PubMed:8824626}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetylputrescine = acetate + putrescine;
CC Xref=Rhea:RHEA:23412, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:58263, ChEBI:CHEBI:326268; EC=3.5.1.62;
CC Evidence={ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetylcadaverine = acetate + cadaverine;
CC Xref=Rhea:RHEA:51892, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:58384, ChEBI:CHEBI:134408;
CC Evidence={ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(1)-acetylspermine = acetate + spermine;
CC Xref=Rhea:RHEA:51896, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:45725, ChEBI:CHEBI:58101;
CC Evidence={ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(1)-acetylspermidine = acetate + spermidine;
CC Xref=Rhea:RHEA:51900, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:57834, ChEBI:CHEBI:58324;
CC Evidence={ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(8)-acetylspermidine = acetate + spermidine;
CC Xref=Rhea:RHEA:23928, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:57834, ChEBI:CHEBI:58535; EC=3.5.1.48;
CC Evidence={ECO:0000269|PubMed:3207420, ECO:0000269|PubMed:8824626};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:21268586, ECO:0000269|PubMed:8824626,
CC ECO:0000305|PubMed:3207420};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:21268586,
CC ECO:0000269|PubMed:26200446, ECO:0000269|PubMed:3207420,
CC ECO:0000269|PubMed:8824626};
CC -!- ACTIVITY REGULATION: Zinc ions inhibit enzyme activity in a dose-
CC dependent manner (PubMed:8824626). Inhibited by KCl at concentrations
CC above 10 mM (PubMed:21268586). Inhibited by o-oxyquinoline in vitro,
CC suggesting that it is a metalloprotein (PubMed:3207420). Inhibited by
CC various substrate N(8)-acetylspermidine analogs bearing different
CC metal-binding groups such as trifluoromethylketone, thiol, or
CC hydroxamate, and by hydroxamate analogs of short-chain acetyldiamines
CC (PubMed:26200446). {ECO:0000269|PubMed:21268586,
CC ECO:0000269|PubMed:26200446, ECO:0000269|PubMed:3207420,
CC ECO:0000269|PubMed:8824626}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for N-acetylcadaverine {ECO:0000269|PubMed:8824626};
CC KM=220 uM for N-acetylputrescine {ECO:0000269|PubMed:8824626};
CC KM=130 uM for N(1)-acetylspermidine {ECO:0000269|PubMed:8824626};
CC KM=310 uM for N(8)-acetylspermidine {ECO:0000269|PubMed:8824626};
CC KM=290 uM for N(1)-acetylspermine {ECO:0000269|PubMed:8824626};
CC Vmax=27 umol/min/mg enzyme with N-acetylcadaverine as substrate
CC {ECO:0000269|PubMed:8824626};
CC Vmax=27 umol/min/mg enzyme with N-acetylputrescine as substrate
CC {ECO:0000269|PubMed:8824626};
CC Vmax=16.5 umol/min/mg enzyme with N(1)-acetylspermidine as substrate
CC {ECO:0000269|PubMed:8824626};
CC Vmax=17.2 umol/min/mg enzyme with N(8)-acetylspermidine as substrate
CC {ECO:0000269|PubMed:8824626};
CC Vmax=13.4 umol/min/mg enzyme with N(1)-acetylspermine as substrate
CC {ECO:0000269|PubMed:8824626};
CC pH dependence:
CC Optimum pH is 9 with acetylputrescine, N(1)-acetylspermidine, and
CC N(8)-acetylspermidine as substrates, and is 8 with acetylcadaverine
CC as substrate. {ECO:0000269|PubMed:3207420};
CC -!- PATHWAY: Amine and polyamine metabolism. {ECO:0000305|PubMed:8824626}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21268586,
CC ECO:0000269|PubMed:3207420}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D10463; BAA01256.1; -; Genomic_DNA.
DR PIR; T48858; T48858.
DR PDB; 3Q9B; X-ray; 2.25 A; A/B/C/D/E/F/G/H/I/J/K/L=1-341.
DR PDB; 3Q9C; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-341.
DR PDB; 3Q9E; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L=1-341.
DR PDB; 3Q9F; X-ray; 2.35 A; A/B/C/D/E/F/G/H/I/J/K/L=1-341.
DR PDB; 4ZUM; X-ray; 1.42 A; A/B=1-341.
DR PDB; 4ZUN; X-ray; 1.40 A; A/B=1-341.
DR PDB; 4ZUO; X-ray; 1.33 A; A/B=1-341.
DR PDB; 4ZUP; X-ray; 1.42 A; A/B=1-341.
DR PDB; 4ZUQ; X-ray; 1.22 A; A/B=1-341.
DR PDB; 4ZUR; X-ray; 1.13 A; A/B=1-341.
DR PDBsum; 3Q9B; -.
DR PDBsum; 3Q9C; -.
DR PDBsum; 3Q9E; -.
DR PDBsum; 3Q9F; -.
DR PDBsum; 4ZUM; -.
DR PDBsum; 4ZUN; -.
DR PDBsum; 4ZUO; -.
DR PDBsum; 4ZUP; -.
DR PDBsum; 4ZUQ; -.
DR PDBsum; 4ZUR; -.
DR AlphaFoldDB; Q48935; -.
DR SMR; Q48935; -.
DR BindingDB; Q48935; -.
DR ChEMBL; CHEMBL1795187; -.
DR BioCyc; MetaCyc:MON-14060; -.
DR BRENDA; 3.5.1.62; 14256.
DR EvolutionaryTrace; Q48935; -.
DR GO; GO:0047609; F:acetylputrescine deacetylase activity; IEA:UniProtKB-EC.
DR GO; GO:0047611; F:acetylspermidine deacetylase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PRINTS; PR01270; HDASUPER.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hydrolase; Metal-binding; Zinc.
FT CHAIN 1..341
FT /note="Acetylpolyamine amidohydrolase"
FT /id="PRO_0000114737"
FT ACT_SITE 159
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:21268586,
FT ECO:0000305|PubMed:26200446"
FT BINDING 19
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0007744|PDB:3Q9E"
FT BINDING 106
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0007744|PDB:3Q9C"
FT BINDING 117
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0007744|PDB:3Q9E"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0000269|PubMed:26200446, ECO:0007744|PDB:3Q9B,
FT ECO:0007744|PDB:3Q9E"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0000269|PubMed:26200446, ECO:0007744|PDB:3Q9B,
FT ECO:0007744|PDB:3Q9E"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0000269|PubMed:26200446, ECO:0007744|PDB:3Q9B,
FT ECO:0007744|PDB:3Q9E"
FT BINDING 323
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21268586,
FT ECO:0007744|PDB:3Q9E"
FT SITE 323
FT /note="Polarizes the scissile carbonyl of the substrate"
FT /evidence="ECO:0000305|PubMed:21268586"
FT MUTAGEN 158
FT /note="H->A: Reduces enzyme activity by 97%."
FT /evidence="ECO:0000269|PubMed:21268586"
FT MUTAGEN 159
FT /note="H->A: Abolishes enzyme activity."
FT MUTAGEN 323
FT /note="Y->F: Reduces enzyme activity by 99%."
FT /evidence="ECO:0000269|PubMed:21268586"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 7..11
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 31..42
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 65..80
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 105..111
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 124..143
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 173..183
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 210..219
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:4ZUQ"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 244..249
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 255..272
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 275..281
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:3Q9C"
FT HELIX 298..309
FT /evidence="ECO:0007829|PDB:4ZUR"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:4ZUR"
FT HELIX 327..340
FT /evidence="ECO:0007829|PDB:4ZUR"
SQ SEQUENCE 341 AA; 36332 MW; 950583DF79059F4A CRC64;
MRVIFSEDHK LRNAKTELYG GELVPPFEAP FRAEWILAAV KEAGFDDVVA PARHGLETVL
KVHDAGYLNF LETAWDRWKA AGYKGEAIAT SFPVRRTSPR IPTDIEGQIG YYCNAAETAI
SPGTWEAALS SMASAIDGAD LIAAGHKAAF SLCRPPGHHA GIDMFGGYCF INNAAVAAQR
LLDKGAKKIA ILDVDFHHGN GTQDIFYERG DVFFASLHGD PAEAFPHFLG YAEETGKGAG
AGTTANYPMG RGTPYSVWGE ALTDSLKRIA AFGAEAIVVS LGVDTFEQDP ISFFKLTSPD
YITMGRTIAA SGVPLLVVME GGYGVPEIGL NVANVLKGVA G
