D89S1_PYRHO
ID D89S1_PYRHO Reviewed; 287 AA.
AC O59272;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Damage-control phosphatase PH1575 {ECO:0000303|PubMed:27322068};
DE EC=3.1.3.- {ECO:0000269|PubMed:27322068};
DE AltName: Full=Nucleotides phosphatase PH1575 {ECO:0000303|PubMed:27322068};
GN OrderedLocusNames=PH1575;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND MUTAGENESIS OF CYS-7; CYS-10;
RP GLN-14; ASN-108; ASP-111; ASP-156; ASN-157; GLU-160; ASP-191; LYS-263 AND
RP CYS-264.
RX PubMed=27322068; DOI=10.1038/nchembio.2108;
RA Huang L., Khusnutdinova A., Nocek B., Brown G., Xu X., Cui H., Petit P.,
RA Flick R., Zallot R., Balmant K., Ziemak M.J., Shanklin J.,
RA de Crecy-Lagard V., Fiehn O., Gregory J.F. III, Joachimiak A.,
RA Savchenko A., Yakunin A.F., Hanson A.D.;
RT "A family of metal-dependent phosphatases implicated in metabolite damage-
RT control.";
RL Nat. Chem. Biol. 12:621-627(2016).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS).
RG Joint Center for Structural Genomics (JCSG);
RT "Crystal structure of hypothetical protein (3258004) from Pyrococcus
RT horikoshii at 2.04 A resolution.";
RL Submitted (MAR-2006) to the PDB data bank.
CC -!- FUNCTION: Metal-dependent phosphatase with probable damage-control
CC functions (PubMed:27322068). Shows phosphatase activity against p-
CC nitrophenyl phosphate (pNPP), but natural substrates have not been
CC identified yet (PubMed:27322068). Low phosphatase activity against 8-
CC oxo nucleotides suggests that it could hydrolyze oxidatively damaged
CC purine nucleotides or their biosynthetic intermediates
CC (PubMed:27322068). {ECO:0000269|PubMed:27322068}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27322068};
CC Name=Ni(2+); Xref=ChEBI:CHEBI:49786;
CC Evidence={ECO:0000269|PubMed:27322068};
CC Note=Phosphatase activity is strongly promoted by several divalent
CC cation ions but is it suggested that Mn(2+) and possibly Ni(2+)
CC represent biologically relevant metal ion cofactors for damage-control
CC phosphatase activity (PubMed:27322068). {ECO:0000269|PubMed:27322068};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:27322068};
CC Note=The [2Fe-2S] cluster does not seem to be directly involved in
CC catalysis (PubMed:27322068). {ECO:0000269|PubMed:27322068};
CC -!- ACTIVITY REGULATION: Activity is strongly promoted by Co(2+), Ni(2+),
CC Mg(2+), Mn(2+), Ca(2+), Zn(2+) and Cu(2+) (PubMed:27322068). Activity
CC is inhibited by EDTA (PubMed:27322068). {ECO:0000269|PubMed:27322068}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=110 uM for p-nitrophenylphosphate {ECO:0000269|PubMed:27322068};
CC KM=600 uM for 8-oxo-2'-deoxyguanosine-5'-triphosphate
CC {ECO:0000269|PubMed:27322068};
CC KM=420 uM for adenosine-5'-diphosphate {ECO:0000269|PubMed:27322068};
CC KM=1.9 uM for Zn(2+) {ECO:0000269|PubMed:27322068};
CC KM=4.6 uM for Ni(2+) {ECO:0000269|PubMed:27322068};
CC Note=kcat is 1.00 sec(-1) with p-nitrophenylphosphate as substrate.
CC kcat is 0.20 sec(-1) with adenosine-5'-diphosphate as substrate. kcat
CC is 0.12 sec(-1) with 8-oxo-2'-deoxyguanosine-5'-triphosphatee as
CC substrate. {ECO:0000269|PubMed:27322068};
CC -!- DOMAIN: Subfamily I proteins are distinguished by three conserved
CC motifs: the CxxC motif localized near the N-terminus, the GNFE motif
CC localized about 40 residues from the C-terminus, and the KC motif
CC localized about 25 residues from the C-terminus (Probable). In the
CC crystal structures of the subfamily I proteins, the side chains of the
CC cysteines in the CxxC and KC motifs face each other across the rim of
CC the putative substrate-binding cleft, and the GNFE motif lies deep in
CC the cleft close to the metal-binding aspartate and asparagine
CC (Probable). the 3 conserved cysteines in motifs CxxC and KC play a key
CC role in the interaction with the Fe-containing chromophore, which is
CC not directly involved in catalysis (Probable).
CC {ECO:0000305|PubMed:27322068}.
CC -!- SIMILARITY: Belongs to the damage-control phosphatase family.
CC Nucleotides phosphatase I subfamily. {ECO:0000305}.
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DR EMBL; BA000001; BAA30687.1; -; Genomic_DNA.
DR PIR; G71035; G71035.
DR RefSeq; WP_010885650.1; NC_000961.1.
DR PDB; 2G8L; X-ray; 2.04 A; A/B=1-287.
DR PDBsum; 2G8L; -.
DR AlphaFoldDB; O59272; -.
DR SMR; O59272; -.
DR STRING; 70601.3258004; -.
DR DNASU; 1443890; -.
DR EnsemblBacteria; BAA30687; BAA30687; BAA30687.
DR GeneID; 1443890; -.
DR KEGG; pho:PH1575; -.
DR eggNOG; arCOG04410; Archaea.
DR OMA; FLLKAKC; -.
DR OrthoDB; 78551at2157; -.
DR EvolutionaryTrace; O59272; -.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR036075; ARMT-1-like_metal-bd_sf.
DR InterPro; IPR002791; ARMT1-like_metal-bd.
DR InterPro; IPR014444; PH1575-like.
DR Pfam; PF01937; ARMT1-like_dom; 1.
DR PIRSF; PIRSF006593; UCP006593; 1.
DR SUPFAM; SSF111321; SSF111321; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Manganese; Metal-binding; Nickel.
FT CHAIN 1..287
FT /note="Damage-control phosphatase PH1575"
FT /id="PRO_0000447506"
FT MOTIF 7..10
FT /note="Subfamily I CxxC motif"
FT /evidence="ECO:0000305|PubMed:27322068"
FT MOTIF 243..246
FT /note="Subfamily I GNFE motif"
FT /evidence="ECO:0000305|PubMed:27322068"
FT MOTIF 263..264
FT /note="Subfamily I KC motif"
FT /evidence="ECO:0000305|PubMed:27322068"
FT BINDING 156
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27322068"
FT BINDING 157
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27322068"
FT BINDING 191
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 7
FT /note="C->A: Does not affect catalytic activity, but
FT abolishes absorption at 300-500 nm."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 10
FT /note="C->A: Does not affect catalytic activity, but
FT abolishes absorption at 300-500 nm."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 14
FT /note="Q->A: Does not affect catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 108
FT /note="N->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 111
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 156
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 157
FT /note="N->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 160
FT /note="E->A: Strongly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 191
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 263
FT /note="K->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27322068"
FT MUTAGEN 264
FT /note="C->A: Does not affect catalytic activity, but
FT abolishes absorption at 300-500 nm."
FT /evidence="ECO:0000269|PubMed:27322068"
FT HELIX 7..22
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 26..43
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 50..65
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 72..92
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 97..109
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 118..129
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 138..147
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 160..174
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:2G8L"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 241..248
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:2G8L"
FT HELIX 265..271
FT /evidence="ECO:0007829|PDB:2G8L"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:2G8L"
SQ SEQUENCE 287 AA; 32555 MW; 6262803C3C60623D CRC64;
MKVQYECLTC MANQCQRIVE MATQDMDIRR RAMILAAKLL AKEYNENAIP AIAGSLIFLE
LYKFLGNDDP FIEYKLKSEE MARKVADIIK RKLKLDFELA VKLAIIGNVI DFSVGFSPED
LEEEVEKMLK DKLYIDDSKE LFEEVKRAEN ILYITDNVGE HYFDAILIEK IREISNAEVY
IAGKEGPIIN DATVEDLKRA GLEKLGKVIS TGTRIVGVPL KLVSREFMEA FNKADVIIAK
GQGNFETLSE INDSRIFFLL KAKCPAVARE LKVPKGALVC MRNKFKL
