HDAH_ALCSD
ID HDAH_ALCSD Reviewed; 369 AA.
AC Q70I53;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Histone deacetylase-like amidohydrolase;
DE Short=HDAC-like amidohydrolase;
DE Short=HDAH;
DE EC=3.5.1.-;
GN Name=hdaH; Synonyms=hdaH1;
OS Alcaligenes sp. (strain DSM 11172) (Bordetella sp. (strain FB188)).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Alcaligenaceae.
OX NCBI_TaxID=242601;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-26; 87-112 AND
RP 304-332, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=15060035; DOI=10.1128/jb.186.8.2328-2339.2004;
RA Hildmann C., Ninkovic M., Dietrich R., Wegener D., Riester D.,
RA Zimmermann T., Birch O.M., Bernegger C., Loidl P., Schwienhorst A.;
RT "A new amidohydrolase from Bordetella or Alcaligenes strain FB188 with
RT similarities to histone deacetylases.";
RL J. Bacteriol. 186:2328-2339(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-369 IN COMPLEXES WITH ZINC AND
RP PHOTOSWITCHABLE PYRAZOLE INHIBITORS, COFACTOR, ACTIVITY REGULATION, AND
RP SUBUNIT.
RX PubMed=27756124; DOI=10.1021/acsinfecdis.6b00148;
RA Weston C.E., Kramer A., Colin F., Yildiz O., Baud M.G., Meyer-Almes F.J.,
RA Fuchter M.J.;
RT "Toward photopharmacological antimicrobial chemotherapy using
RT photoswitchable amidohydrolase inhibitors.";
RL ACS Infect. Dis. 3:152-161(2017).
CC -!- FUNCTION: Exhibits significant levels of protein deacetylase activity
CC comparable to those of eukaryotic HDACs in assays both with fluorogenic
CC peptidic substrates and acetate-radiolabeled histones. Accepts proteins
CC with epsilon-acetylated lysine residues and tritiated-acetate-
CC prelabeled chicken histones as substrates. The natural substrate
CC protein is not yet known. {ECO:0000269|PubMed:15060035}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:27756124};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:27756124};
CC -!- ACTIVITY REGULATION: Zinc, and cobalt and nickel at a lesser extent,
CC are able to increase the catalytic activity (2.2-, 1.3- and 1.1-fold
CC respectively) at concentrations of 1 mM. Higher concentrations have an
CC inhibitory effect. Magnesium, manganese and calcium have no effect on
CC activity at concentrations between 0 and 10 mM. At 100 mM, the
CC catalytic activity is increased between 1.2- and 2.1-fold. Hydroxamates
CC like TSA and SAHA inhibit the enzyme (PubMed:15060035). Is also
CC inhibited by azobenzenes, stilbenes and arylazopyrazoles
CC (PubMed:27756124). {ECO:0000269|PubMed:15060035,
CC ECO:0000269|PubMed:27756124}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:15060035};
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000305|PubMed:27756124}.
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; AJ580773; CAE45336.1; -; Genomic_DNA.
DR PDB; 1ZZ0; X-ray; 1.60 A; A/B/C/D=1-369.
DR PDB; 1ZZ1; X-ray; 1.57 A; A/B/C/D=1-369.
DR PDB; 1ZZ3; X-ray; 1.76 A; A/B/C/D=1-369.
DR PDB; 2GH6; X-ray; 2.20 A; A/B/C/D=2-369.
DR PDB; 2VCG; X-ray; 1.90 A; A/B/C/D=2-369.
DR PDB; 5G17; X-ray; 1.51 A; A/B=2-369.
DR PDB; 5G1A; X-ray; 1.42 A; A/B=2-369.
DR PDB; 5G1B; X-ray; 1.70 A; A/B=2-369.
DR PDB; 5G1C; X-ray; 1.81 A; A/B=2-369.
DR PDB; 5G3W; X-ray; 1.60 A; A/B/C/D=2-369.
DR PDB; 6GJK; X-ray; 1.47 A; A/B=2-369.
DR PDBsum; 1ZZ0; -.
DR PDBsum; 1ZZ1; -.
DR PDBsum; 1ZZ3; -.
DR PDBsum; 2GH6; -.
DR PDBsum; 2VCG; -.
DR PDBsum; 5G17; -.
DR PDBsum; 5G1A; -.
DR PDBsum; 5G1B; -.
DR PDBsum; 5G1C; -.
DR PDBsum; 5G3W; -.
DR PDBsum; 6GJK; -.
DR AlphaFoldDB; Q70I53; -.
DR SMR; Q70I53; -.
DR BindingDB; Q70I53; -.
DR ChEMBL; CHEMBL6017; -.
DR DrugBank; DB07553; 9,9,9-TRIFLUORO-8-OXO-N-PHENYLNONANAMIDE.
DR DrugBank; DB08505; methyl 4-bromo-N-[8-(hydroxyamino)-8-oxooctanoyl]-L-phenylalaninate.
DR DrugCentral; Q70I53; -.
DR BRENDA; 3.5.1.4; 236.
DR BRENDA; 3.5.1.98; 236.
DR EvolutionaryTrace; Q70I53; -.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
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 INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15060035"
FT CHAIN 2..369
FT /note="Histone deacetylase-like amidohydrolase"
FT /id="PRO_0000114728"
FT ACT_SITE 143
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q48935"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27756124,
FT ECO:0007744|PDB:5G1C"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27756124,
FT ECO:0007744|PDB:5G1C"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:27756124,
FT ECO:0007744|PDB:5G1C"
FT SITE 312
FT /note="Polarizes the scissile carbonyl of the substrate"
FT /evidence="ECO:0000250|UniProtKB:Q48935"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 9..13
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 18..22
FT /evidence="ECO:0007829|PDB:5G1A"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 41..52
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 69..73
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:1ZZ3"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:1ZZ3"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 108..126
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 157..167
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 185..190
FT /evidence="ECO:0007829|PDB:5G1A"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 249..256
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 282..299
FT /evidence="ECO:0007829|PDB:5G1A"
FT STRAND 304..308
FT /evidence="ECO:0007829|PDB:5G1A"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 317..329
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 339..343
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 352..358
FT /evidence="ECO:0007829|PDB:5G1A"
FT HELIX 362..367
FT /evidence="ECO:0007829|PDB:5G1A"
SQ SEQUENCE 369 AA; 39424 MW; 25A8C71FFF7C9FE7 CRC64;
MAIGYVWNTL YGWVDTGTGS LAAANLTARM QPISHHLAHP DTKRRFHELV CASGQIEHLT
PIAAVAATDA DILRAHSAAH LENMKRVSNL PTGGDTGDGI TMMGNGGLEI ARLSAGGAVE
LTRRVATGEL SAGYALVNPP GHHAPHNAAM GFCIFNNTSV AAGYARAVLG MERVAILDWD
VHHGNGTQDI WWNDPSVLTI SLHQHLCFPP DSGYSTERGA GNGHGYNINV PLPPGSGNAA
YLHAMDQVVL HALRAYRPQL IIVGSGFDAS MLDPLARMMV TADGFRQMAR RTIDCAADIC
DGRIVFVQEG GYSPHYLPFC GLAVIEELTG VRSLPDPYHE FLAGMGGNTL LDAERAAIEE
IVPLLADIR
