IXTPA_METJA
ID IXTPA_METJA Reviewed; 185 AA.
AC Q57679;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=dITP/XTP pyrophosphatase {ECO:0000305|PubMed:11452035};
DE EC=3.6.1.66 {ECO:0000269|PubMed:11452035};
DE AltName: Full=Hypoxanthine/xanthine dNTP pyrophosphatase {ECO:0000303|PubMed:11452035};
DE AltName: Full=Non-canonical purine NTP pyrophosphatase {ECO:0000305|PubMed:11452035};
DE AltName: Full=Non-standard purine NTP pyrophosphatase {ECO:0000305|PubMed:11452035};
DE AltName: Full=Nucleoside-triphosphate diphosphatase {ECO:0000305|PubMed:10404228};
DE AltName: Full=Nucleoside-triphosphate pyrophosphatase {ECO:0000303|PubMed:10404228};
DE Short=NTPase {ECO:0000303|PubMed:10404228};
DE AltName: Full=Nucleotide triphosphatase {ECO:0000303|PubMed:10404228};
GN OrderedLocusNames=MJ0226;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND COFACTOR.
RX PubMed=11452035; DOI=10.1093/nar/29.14.3099;
RA Chung J.H., Back J.H., Park Y.I., Han Y.S.;
RT "Biochemical characterization of a novel hypoxanthine/xanthine dNTP
RT pyrophosphatase from Methanococcus jannaschii.";
RL Nucleic Acids Res. 29:3099-3107(2001).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH ATP
RP ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=10404228; DOI=10.1038/10745;
RA Hwang K.Y., Chung J.H., Kim S.-H., Han Y.S., Cho Y.;
RT "Structure-based identification of a novel NTPase from Methanococcus
RT jannaschii.";
RL Nat. Struct. Biol. 6:691-696(1999).
CC -!- FUNCTION: Pyrophosphatase that catalyzes the hydrolysis of nucleoside
CC triphosphates to their monophosphate derivatives, with a high
CC preference for the non-canonical purine nucleotides xanthosine
CC triphosphate (XTP), deoxyinosine triphosphate (dITP) and ITP
CC (PubMed:10404228, PubMed:11452035). Probably functions as a house-
CC cleaning enzyme that removes non-canonical purine nucleotides from the
CC nucleotide pool, thus preventing their incorporation into DNA/RNA and
CC avoiding chromosomal lesions (PubMed:11452035). Shows very low activity
CC on GTP or dGTP, both of which are hydrolyzed more than 100-fold less
CC efficiently than XTP, and has nearly no activity toward the canonical
CC nucleotides ATP, CTP, and TTP, and toward 6-N-hydroxylaminopurine
CC deoxynucleoside triphosphate (dHAPTP) (PubMed:10404228,
CC PubMed:11452035). Displays neither endonuclease nor 3'-exonuclease
CC activities (PubMed:11452035). {ECO:0000269|PubMed:10404228,
CC ECO:0000269|PubMed:11452035}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + XTP = diphosphate + H(+) + XMP; Xref=Rhea:RHEA:28610,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57464, ChEBI:CHEBI:61314; EC=3.6.1.66;
CC Evidence={ECO:0000269|PubMed:10404228, ECO:0000269|PubMed:11452035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dITP + H2O = dIMP + diphosphate + H(+); Xref=Rhea:RHEA:28342,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:61194, ChEBI:CHEBI:61382; EC=3.6.1.66;
CC Evidence={ECO:0000269|PubMed:11452035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + ITP = diphosphate + H(+) + IMP; Xref=Rhea:RHEA:29399,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58053, ChEBI:CHEBI:61402; EC=3.6.1.66;
CC Evidence={ECO:0000269|PubMed:10404228, ECO:0000269|PubMed:11452035};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10404228, ECO:0000269|PubMed:11452035};
CC Note=Binds 1 Mg(2+) ion per subunit (By similarity). Magnesium ions are
CC required for optimal activity, with Mn(2+), Zn(2+) and Ni(2+)
CC supporting <50% of the maximum rate (PubMed:11452035).
CC {ECO:0000255|HAMAP-Rule:MF_01405, ECO:0000269|PubMed:10404228,
CC ECO:0000269|PubMed:11452035};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.10 mM for XTP (at pH 7.6 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:10404228};
CC KM=0.15 mM for ITP (at pH 7.6 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:10404228};
CC KM=1.11 mM for GTP (at pH 7.6 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:10404228};
CC KM=1.13 mM for dGTP (at pH 7.6 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:10404228};
CC KM=0.22 mM for XTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=0.25 mM for dITP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=0.24 mM for ITP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=2.12 mM for dGTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=1.94 mM for GTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=2.87 mM for 3'dGTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=2.78 mM for ddGTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=7.3 mM for dATP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=5.47 mM for dCTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=4.4 mM for dTTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=4.22 mM for dUTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=5.3 mM for 8-oxo-dGTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC KM=3.3 mM for dHAPTP (at pH 10.5 and 80 degrees Celsius)
CC {ECO:0000269|PubMed:11452035};
CC Note=kcat is 1009 sec(-1) with XTP as substrate. kcat is 911.7 sec(-
CC 1) with ITP as substrate. kcat is 97.6 sec(-1) with GTP as substrate.
CC kcat is 96.6 sec(-1) with dGTP as substrate (at pH 7.6 and 80 degrees
CC Celsius) (PubMed:10404228). kcat is 176.4 sec(-1) with XTP as
CC substrate. kcat is 152.4 sec(-1) with dITP as substrate. kcat is
CC 155.8 sec(-1) with ITP as substrate. kcat is 9.3 sec(-1) with dGTP as
CC substrate. kcat is 9.1 sec(-1) with GTP as substrate. kcat is 8.2
CC sec(-1) with 3'dGTP as substrate. kcat is 3.3 sec(-1) with ddGTP as
CC substrate. kcat is 0.44 sec(-1) with dATP as substrate. kcat is 0.44
CC sec(-1) with dCTP as substrate. kcat is 1.8 sec(-1) with dTTP as
CC substrate. kcat is 5.8 sec(-1) with dUTP as substrate. kcat is 2.4
CC sec(-1) with 8-oxo-dGTP as substrate. kcat is 1.8 sec(-1) with dHAPTP
CC as substrate (at pH 10.5 and 80 degrees Celsius) (PubMed:11452035).
CC {ECO:0000269|PubMed:10404228, ECO:0000269|PubMed:11452035};
CC pH dependence:
CC Optimum pH is 10.5 with dITP as substrate. The reaction rates under
CC neutral conditions are <30% of maximum.
CC {ECO:0000269|PubMed:11452035};
CC Temperature dependence:
CC Optimum temperature is 80 degrees Celsius. At low temperature (30
CC degrees Celsius), shows about 5-fold decrease in activity compared to
CC the maximum activity at 80 degrees Celsius. Is highly thermostable.
CC The half-life of the protein at 95 degrees Celsius is about 200
CC minutes. {ECO:0000269|PubMed:11452035};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10404228}.
CC -!- SIMILARITY: Belongs to the HAM1 NTPase family. {ECO:0000255|HAMAP-
CC Rule:MF_01405}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB98211.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L77117; AAB98211.1; ALT_INIT; Genomic_DNA.
DR PIR; C64328; C64328.
DR RefSeq; WP_064496428.1; NC_000909.1.
DR PDB; 1B78; X-ray; 2.20 A; A/B=1-185.
DR PDB; 2MJP; X-ray; 2.20 A; A/B=1-185.
DR PDBsum; 1B78; -.
DR PDBsum; 2MJP; -.
DR AlphaFoldDB; Q57679; -.
DR SMR; Q57679; -.
DR STRING; 243232.MJ_0226; -.
DR EnsemblBacteria; AAB98211; AAB98211; MJ_0226.
DR GeneID; 1451077; -.
DR KEGG; mja:MJ_0226; -.
DR eggNOG; arCOG04184; Archaea.
DR HOGENOM; CLU_082080_1_0_2; -.
DR InParanoid; Q57679; -.
DR OrthoDB; 94889at2157; -.
DR BRENDA; 3.6.1.66; 3260.
DR SABIO-RK; Q57679; -.
DR EvolutionaryTrace; Q57679; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0035870; F:dITP diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0036220; F:ITP diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:InterPro.
DR GO; GO:0047429; F:nucleoside-triphosphate diphosphatase activity; IBA:GO_Central.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0036222; F:XTP diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0009146; P:purine nucleoside triphosphate catabolic process; IDA:UniProtKB.
DR CDD; cd00515; HAM1; 1.
DR Gene3D; 3.90.950.10; -; 1.
DR HAMAP; MF_01405; Non_canon_purine_NTPase; 1.
DR InterPro; IPR020922; dITP/XTP_pyrophosphatase.
DR InterPro; IPR002637; Ham1p-like.
DR InterPro; IPR029001; ITPase-like_fam.
DR PANTHER; PTHR11067; PTHR11067; 1.
DR Pfam; PF01725; Ham1p_like; 1.
DR SUPFAM; SSF52972; SSF52972; 1.
DR TIGRFAMs; TIGR00042; TIGR00042; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Magnesium; Metal-binding; Nucleotide metabolism;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..185
FT /note="dITP/XTP pyrophosphatase"
FT /id="PRO_0000178274"
FT ACT_SITE 65
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 7..12
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 37
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 65
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 66
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 141..144
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 164
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405"
FT BINDING 169..170
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01405,
FT ECO:0000305|PubMed:10404228, ECO:0007744|PDB:2MJP"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 10..19
FT /evidence="ECO:0007829|PDB:1B78"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:1B78"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:1B78"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 42..57
FT /evidence="ECO:0007829|PDB:1B78"
FT STRAND 61..70
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 81..87
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 89..97
FT /evidence="ECO:0007829|PDB:1B78"
FT STRAND 104..115
FT /evidence="ECO:0007829|PDB:1B78"
FT STRAND 118..130
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:1B78"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:1B78"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:1B78"
FT HELIX 169..182
FT /evidence="ECO:0007829|PDB:1B78"
SQ SEQUENCE 185 AA; 21273 MW; 97EC2DA5C0D21D67 CRC64;
MKIYFATGNP NKIKEANIIL KDLKDVEIEQ IKISYPEIQG TLEEVAEFGA KWVYNILKKP
VIVEDSGFFV EALNGFPGTY SKFVQETIGN EGILKLLEGK DNRNAYFKTV IGYCDENGVR
LFKGIVKGRV SEEIRSKGYG FAYDSIFIPE EEERTFAEMT TEEKSQISHR KKAFEEFKKF
LLDRI
