ADPP_MYCTU
ID ADPP_MYCTU Reviewed; 207 AA.
AC I6X235;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=ADP-ribose pyrophosphatase {ECO:0000305};
DE EC=3.6.1.13 {ECO:0000269|PubMed:27683242};
DE AltName: Full=8-oxo-(d)GDP phosphatase {ECO:0000305};
DE EC=3.6.1.58 {ECO:0000269|PubMed:23463507};
DE AltName: Full=ADPR hydrolase {ECO:0000303|PubMed:27683242};
DE AltName: Full=MT-ADPRase {ECO:0000303|PubMed:12906832};
GN OrderedLocusNames=Rv1700 {ECO:0000312|EMBL:CCP44465.1};
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2] {ECO:0007744|PubMed:21969609}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=H37Rv;
RX PubMed=23463507; DOI=10.1074/jbc.m112.442566;
RA Patil A.G., Sang P.B., Govindan A., Varshney U.;
RT "Mycobacterium tuberculosis MutT1 (Rv2985) and ADPRase (Rv1700) proteins
RT constitute a two-stage mechanism of 8-oxo-dGTP and 8-oxo-GTP detoxification
RT and adenosine to cytidine mutation avoidance.";
RL J. Biol. Chem. 288:11252-11262(2013).
RN [4] {ECO:0007744|PDB:1MK1, ECO:0007744|PDB:1MP2, ECO:0007744|PDB:1MQE, ECO:0007744|PDB:1MQW, ECO:0007744|PDB:1MR2}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEXES WITH ADPR AND
RP MANGANESE, COFACTOR, AND ACTIVE SITE.
RX PubMed=12906832; DOI=10.1016/s0969-2126(03)00154-0;
RA Kang L.W., Gabelli S.B., Cunningham J.E., O'Handley S.F., Amzel L.M.;
RT "Structure and mechanism of MT-ADPRase, a nudix hydrolase from
RT Mycobacterium tuberculosis.";
RL Structure 11:1015-1023(2003).
RN [5] {ECO:0007744|PDB:5I8U}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF MUTANT GLN-142, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE,
RP AND MUTAGENESIS OF ARG-64; GLU-93; GLU-97 AND GLU-142.
RX PubMed=27683242; DOI=10.1007/s10863-016-9681-9;
RA O'Handley S.F., Thirawatananond P., Kang L.W., Cunningham J.E., Leyva J.A.,
RA Amzel L.M., Gabelli S.B.;
RT "Kinetic and mutational studies of the adenosine diphosphate ribose
RT hydrolase from Mycobacterium tuberculosis.";
RL J. Bioenerg. Biomembr. 48:557-567(2016).
CC -!- FUNCTION: Catalyzes the hydrolysis of ADP-ribose (ADPR) to AMP and
CC ribose-5-phosphate. Can also hydrolyze ADP-mannose and ADP-glucose,
CC with lower efficiency. Has weaker activity with NAD, GDP-sugars and
CC UDP-sugars (PubMed:27683242). Also catalyzes the conversion of 8-oxo-
CC dGDP to 8-oxo-dGMP, and 8-oxo-GDP to 8-oxo-GMP. Functions in concert
CC with MutT1 to detoxify 8-oxo-dGTP to 8-oxo-dGMP and may play an
CC important role in supporting cellular growth under oxidative stress
CC (PubMed:23463507). The catalytic efficiency is much higher for the
CC hydrolysis of ADPR than 8-oxo-dGTP, suggesting a more relevant
CC biological role in hydrolysis of ADPR (PubMed:27683242).
CC {ECO:0000269|PubMed:23463507, ECO:0000269|PubMed:27683242}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-D-ribose + H2O = AMP + D-ribose 5-phosphate + 2 H(+);
CC Xref=Rhea:RHEA:10412, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57967, ChEBI:CHEBI:78346, ChEBI:CHEBI:456215;
CC EC=3.6.1.13; Evidence={ECO:0000269|PubMed:27683242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-oxo-dGDP + H2O = 8-oxo-dGMP + H(+) + phosphate;
CC Xref=Rhea:RHEA:32063, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:63224, ChEBI:CHEBI:63715; EC=3.6.1.58;
CC Evidence={ECO:0000269|PubMed:23463507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-oxo-GDP + H2O = 8-oxo-GMP + H(+) + phosphate;
CC Xref=Rhea:RHEA:62356, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:143554, ChEBI:CHEBI:145694;
CC EC=3.6.1.58; Evidence={ECO:0000269|PubMed:23463507};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12906832, ECO:0000269|PubMed:27683242};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27683242};
CC Note=Binds 3 Mg(2+) ions per subunit (PubMed:12906832). Activity is
CC highest with Mn(2+). Can also use Zn(2+) or Co(2+), with lower
CC efficiency (PubMed:27683242). {ECO:0000269|PubMed:12906832,
CC ECO:0000269|PubMed:27683242};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=200 uM for ADPR (in the presence of Mg(2+) ions)
CC {ECO:0000269|PubMed:27683242};
CC KM=554 uM for ADPR (in the presence of Mn(2+) ions)
CC {ECO:0000269|PubMed:27683242};
CC KM=9.5 uM for 8-oxo-dGDP {ECO:0000269|PubMed:23463507};
CC Vmax=0.04 pmol/min/ng enzyme with 8-oxo-dGDP as substrate
CC {ECO:0000269|PubMed:23463507};
CC Note=kcat is 14.4 sec(-1) with ADPR as substrate (in the presence of
CC Mg(2+) ions). kcat is 28.9 sec(-1) with ADPR as substrate (in the
CC presence of Mn(2+) ions) (PubMed:27683242). kcat is 0.0164 sec(-1)
CC with 8-oxo-dGDP as substrate (PubMed:23463507).
CC {ECO:0000269|PubMed:23463507, ECO:0000269|PubMed:27683242};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:27683242};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12906832}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44465.1; -; Genomic_DNA.
DR RefSeq; NP_216216.1; NC_000962.3.
DR RefSeq; WP_003408399.1; NZ_NVQJ01000010.1.
DR PDB; 1MK1; X-ray; 2.00 A; A=1-207.
DR PDB; 1MP2; X-ray; 2.30 A; A=1-207.
DR PDB; 1MQE; X-ray; 2.00 A; A=1-207.
DR PDB; 1MQW; X-ray; 2.30 A; A=1-207.
DR PDB; 1MR2; X-ray; 2.30 A; A=1-207.
DR PDB; 5I8U; X-ray; 2.00 A; A/B/C/D/E/F/G=1-207.
DR PDBsum; 1MK1; -.
DR PDBsum; 1MP2; -.
DR PDBsum; 1MQE; -.
DR PDBsum; 1MQW; -.
DR PDBsum; 1MR2; -.
DR PDBsum; 5I8U; -.
DR AlphaFoldDB; I6X235; -.
DR SMR; I6X235; -.
DR STRING; 83332.Rv1700; -.
DR PaxDb; I6X235; -.
DR PRIDE; I6X235; -.
DR DNASU; 885049; -.
DR GeneID; 45425669; -.
DR GeneID; 885049; -.
DR KEGG; mtu:Rv1700; -.
DR PATRIC; fig|83332.111.peg.1888; -.
DR TubercuList; Rv1700; -.
DR eggNOG; COG0494; Bacteria.
DR OMA; DYQVHPG; -.
DR PhylomeDB; I6X235; -.
DR BioCyc; MetaCyc:G185E-5891-MON; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0044715; F:8-oxo-dGDP phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0044716; F:8-oxo-GDP phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0047631; F:ADP-ribose diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0006753; P:nucleoside phosphate metabolic process; IBA:GO_Central.
DR GO; GO:0019693; P:ribose phosphate metabolic process; IBA:GO_Central.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR Pfam; PF00293; NUDIX; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; DNA replication; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Reference proteome.
FT CHAIN 1..207
FT /note="ADP-ribose pyrophosphatase"
FT /id="PRO_0000449350"
FT DOMAIN 41..172
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 77..99
FT /note="Nudix box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT ACT_SITE 142
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:12906832,
FT ECO:0000305|PubMed:27683242"
FT BINDING 37..38
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q93K97"
FT BINDING 64
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 78
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 114..116
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q93K97"
FT BINDING 120
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:12906832"
FT BINDING 142
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12906832"
FT MUTAGEN 64
FT /note="R->A: 3-fold decrease in KM for ADPR. 910-fold
FT decrease in kcat with ADPR as substrate."
FT /evidence="ECO:0000269|PubMed:27683242"
FT MUTAGEN 93
FT /note="E->Q: 2.1-fold decrease in KM for ADPR. 1940-fold
FT decrease in kcat with ADPR as substrate."
FT /evidence="ECO:0000269|PubMed:27683242"
FT MUTAGEN 97
FT /note="E->Q: 2.3-fold decrease in KM for ADPR. 1150-fold
FT decrease in kcat with ADPR as substrate."
FT /evidence="ECO:0000269|PubMed:27683242"
FT MUTAGEN 142
FT /note="E->Q: 2.7-fold decrease in KM for ADPR. 300-fold
FT decrease in kcat with ADPR as substrate."
FT /evidence="ECO:0000269|PubMed:27683242"
FT STRAND 7..16
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 18..28
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 34..42
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:5I8U"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:5I8U"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 100..113
FT /evidence="ECO:0007829|PDB:5I8U"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 121..132
FT /evidence="ECO:0007829|PDB:5I8U"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:5I8U"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:5I8U"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:5I8U"
FT HELIX 199..204
FT /evidence="ECO:0007829|PDB:5I8U"
SQ SEQUENCE 207 AA; 22893 MW; 7FB78C9C984FA85E CRC64;
MAEHDFETIS SETLHTGAIF ALRRDQVRMP GGGIVTREVV EHFGAVAIVA MDDNGNIPMV
YQYRHTYGRR LWELPAGLLD VAGEPPHLTA ARELREEVGL QASTWQVLVD LDTAPGFSDE
SVRVYLATGL REVGRPEAHH EEADMTMGWY PIAEAARRVL RGEIVNSIAI AGVLAVHAVT
TGFAQPRPLD TEWIDRPTAF AARRAER
