ADA_PLAVS
ID ADA_PLAVS Reviewed; 363 AA.
AC A5KE01;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Adenosine deaminase {ECO:0000305};
DE EC=3.5.4.4 {ECO:0000269|PubMed:19728741};
DE AltName: Full=S-methyl-5'-thioadenosine deaminase {ECO:0000305};
DE EC=3.5.4.31 {ECO:0000269|PubMed:19728741};
GN Name=ADA {ECO:0000305}; ORFNames=PVX_111245 {ECO:0000312|EMBL:EDL42450.1};
OS Plasmodium vivax (strain Salvador I).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=126793 {ECO:0000312|Proteomes:UP000008333};
RN [1] {ECO:0000312|Proteomes:UP000008333}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Salvador I {ECO:0000312|Proteomes:UP000008333};
RX PubMed=18843361; DOI=10.1038/nature07327;
RA Carlton J.M., Adams J.H., Silva J.C., Bidwell S.L., Lorenzi H., Caler E.,
RA Crabtree J., Angiuoli S.V., Merino E.F., Amedeo P., Cheng Q.,
RA Coulson R.M.R., Crabb B.S., del Portillo H.A., Essien K., Feldblyum T.V.,
RA Fernandez-Becerra C., Gilson P.R., Gueye A.H., Guo X., Kang'a S.,
RA Kooij T.W.A., Korsinczky M., Meyer E.V.-S., Nene V., Paulsen I., White O.,
RA Ralph S.A., Ren Q., Sargeant T.J., Salzberg S.L., Stoeckert C.J.,
RA Sullivan S.A., Yamamoto M.M., Hoffman S.L., Wortman J.R., Gardner M.J.,
RA Galinski M.R., Barnwell J.W., Fraser-Liggett C.M.;
RT "Comparative genomics of the neglected human malaria parasite Plasmodium
RT vivax.";
RL Nature 455:757-763(2008).
RN [2] {ECO:0007744|PDB:2PGF, ECO:0007744|PDB:2PGR, ECO:0007744|PDB:2QVN}
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) IN COMPLEX WITH ZINC; ADENOSINE;
RP GUANOSINE AND INHIBITOR PENTOSTATIN.
RX PubMed=18602399; DOI=10.1016/j.jmb.2008.06.048;
RA Larson E.T., Deng W., Krumm B.E., Napuli A., Mueller N., Van Voorhis W.C.,
RA Buckner F.S., Fan E., Lauricella A., DeTitta G., Luft J., Zucker F.,
RA Hol W.G., Verlinde C.L., Merritt E.A.;
RT "Structures of substrate- and inhibitor-bound adenosine deaminase from a
RT human malaria parasite show a dramatic conformational change and shed light
RT on drug selectivity.";
RL J. Mol. Biol. 381:975-988(2008).
RN [3] {ECO:0007744|PDB:3EWC, ECO:0007744|PDB:3EWD}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANT ASP-172 DEL IN COMPLEX
RP WITH ZINC AND INHIBITOR METHYLTHIOCOFORMYCIN, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP MUTAGENESIS OF ASP-172.
RX PubMed=19728741; DOI=10.1021/bi9012484;
RA Ho M.C., Cassera M.B., Madrid D.C., Ting L.M., Tyler P.C., Kim K.,
RA Almo S.C., Schramm V.L.;
RT "Structural and metabolic specificity of methylthiocoformycin for malarial
RT adenosine deaminases.";
RL Biochemistry 48:9618-9626(2009).
CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine to produce
CC inosine (PubMed:19728741). Unlike mammalian adenosine deaminases, also
CC catalyzes the deamination of 5'-methylthioadenosine (MTA), a by-product
CC of polyamine biosynthesis, to produce 5'-methylthioinosine (MTI)
CC (PubMed:19728741). Plays an essential role in the purine salvage
CC pathway which allows the parasite to use host cell purines for the
CC synthesis of nucleic acids (PubMed:19728741).
CC {ECO:0000269|PubMed:19728741}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + H(+) + H2O = inosine + NH4(+);
CC Xref=Rhea:RHEA:24408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:28938; EC=3.5.4.4;
CC Evidence={ECO:0000269|PubMed:19728741};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O + S-methyl-5'-thioadenosine = NH4(+) + S-methyl-5'-
CC thioinosine; Xref=Rhea:RHEA:25025, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:48595; EC=3.5.4.31;
CC Evidence={ECO:0000269|PubMed:19728741};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:18602399, ECO:0000305|PubMed:19728741};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18602399,
CC ECO:0000269|PubMed:19728741};
CC -!- ACTIVITY REGULATION: Inhibited by coformycin and methylthiocoformycin
CC (MT-coformycin). {ECO:0000269|PubMed:19728741}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=60 uM for adenosine (at pH 8) {ECO:0000269|PubMed:19728741};
CC KM=9.5 uM for 5'-methylthioadenosine (MTA) (at pH 8)
CC {ECO:0000269|PubMed:19728741};
CC Note=kcat is 1.8 sec(-1) with adenosine as substrate
CC (PubMed:19728741). kcat is 0.13 sec(-1) with 5'-methylthioadenosine
CC as substrate (PubMed:19728741). {ECO:0000269|PubMed:19728741};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000269|PubMed:19728741}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Adenosine and AMP deaminases family. {ECO:0000305}.
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DR EMBL; AAKM01002769; EDL42450.1; -; Genomic_DNA.
DR RefSeq; XP_001608474.1; XM_001608424.1.
DR PDB; 2PGF; X-ray; 1.89 A; A=1-363.
DR PDB; 2PGR; X-ray; 2.30 A; A=1-363.
DR PDB; 2QVN; X-ray; 2.19 A; A=1-363.
DR PDB; 3EWC; X-ray; 2.11 A; A=1-363.
DR PDB; 3EWD; X-ray; 1.90 A; A=1-363.
DR PDBsum; 2PGF; -.
DR PDBsum; 2PGR; -.
DR PDBsum; 2QVN; -.
DR PDBsum; 3EWC; -.
DR PDBsum; 3EWD; -.
DR AlphaFoldDB; A5KE01; -.
DR SMR; A5KE01; -.
DR STRING; 126793.A5KE01; -.
DR EnsemblProtists; EDL42450; EDL42450; PVX_111245.
DR GeneID; 5471345; -.
DR KEGG; pvx:PVX_111245; -.
DR VEuPathDB; PlasmoDB:PVX_111245; -.
DR InParanoid; A5KE01; -.
DR OMA; NHFTIHA; -.
DR PhylomeDB; A5KE01; -.
DR UniPathway; UPA00606; -.
DR EvolutionaryTrace; A5KE01; -.
DR Proteomes; UP000008333; Chromosome 6.
DR Proteomes; UP000008333; Unassembled WGS sequence.
DR GO; GO:0090614; F:5'-methylthioadenosine deaminase activity; IDA:UniProtKB.
DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009168; P:purine ribonucleoside monophosphate biosynthetic process; IEA:InterPro.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR InterPro; IPR006650; A/AMP_deam_AS.
DR InterPro; IPR001365; A_deaminase_dom.
DR InterPro; IPR006330; Ado/ade_deaminase.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR11409; PTHR11409; 1.
DR Pfam; PF00962; A_deaminase; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR PROSITE; PS00485; A_DEAMINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Purine salvage; Reference proteome;
KW Zinc.
FT CHAIN 1..363
FT /note="Adenosine deaminase"
FT /id="PRO_0000451865"
FT REGION 170..184
FT /note="Gating helix loop; regulates binding affinity for
FT substrates and thus substrate selectivity"
FT /evidence="ECO:0000305|PubMed:18602399"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:3EWC,
FT ECO:0007744|PDB:3EWD"
FT BINDING 44..46
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0007744|PDB:2PGF, ECO:0007744|PDB:2PGR,
FT ECO:0007744|PDB:2QVN"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:3EWC,
FT ECO:0007744|PDB:3EWD"
FT BINDING 172
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:2QVN,
FT ECO:0007744|PDB:3EWC"
FT BINDING 201
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:2QVN,
FT ECO:0007744|PDB:3EWD"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:3EWC,
FT ECO:0007744|PDB:3EWD"
FT BINDING 229
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:2QVN,
FT ECO:0007744|PDB:3EWC, ECO:0007744|PDB:3EWD"
FT BINDING 253
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:3EWC,
FT ECO:0007744|PDB:3EWD"
FT BINDING 310
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:2QVN,
FT ECO:0007744|PDB:3EWD"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18602399,
FT ECO:0000269|PubMed:19728741, ECO:0007744|PDB:2PGF,
FT ECO:0007744|PDB:2PGR, ECO:0007744|PDB:3EWC,
FT ECO:0007744|PDB:3EWD"
FT SITE 172
FT /note="Important for substrate specificity for S-methyl-5'-
FT thioadenosine"
FT /evidence="ECO:0000269|PubMed:19728741"
FT MUTAGEN 172
FT /note="D->A: Loss of S-methyl-5'-thioadenosine deaminase
FT activity. Slight decrease in adenosine deaminase activity."
FT /evidence="ECO:0000269|PubMed:19728741"
FT MUTAGEN 172
FT /note="D->E: Loss of S-methyl-5'-thioadenosine deaminase
FT activity. Slight decrease in adenosine deaminase activity."
FT /evidence="ECO:0000269|PubMed:19728741"
FT MUTAGEN 172
FT /note="Missing: Loss of S-methyl-5'-thioadenosine deaminase
FT activity. No effect on adenosine deaminase activity."
FT /evidence="ECO:0000269|PubMed:19728741"
FT HELIX 13..18
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 38..44
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 85..95
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 102..119
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 121..128
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 130..134
FT /evidence="ECO:0007829|PDB:2PGF"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 141..158
FT /evidence="ECO:0007829|PDB:2PGF"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 162..175
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 180..189
FT /evidence="ECO:0007829|PDB:2PGF"
FT TURN 190..193
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 194..202
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 210..218
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 233..236
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 237..244
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 255..259
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 261..269
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 295..300
FT /evidence="ECO:0007829|PDB:2PGF"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 319..330
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 334..347
FT /evidence="ECO:0007829|PDB:2PGF"
FT HELIX 352..362
FT /evidence="ECO:0007829|PDB:2PGF"
SQ SEQUENCE 363 AA; 41871 MW; 951357683E2964C1 CRC64;
MNILQEPIDF LKKEELKNID LSQMSKKERY KIWKRIPKCE LHCHLDLCFS ADFFVSCIRK
YNLQPNLSDE EVLDYYLFAK GGKSLGEFVE KAIKVADIFH DYEVIEDLAK HAVFNKYKEG
VVLMEFRYSP TFVAFKYNLD IELIHQAIVK GIKEVVELLD HKIHVALMCI GDTGHEAANI
KASADFCLKH KADFVGFDHG GHEVDLKEYK EIFDYVRESG VPLSVHAGED VTLPNLNTLY
SAIQVLKVER IGHGIRVAES QELIDMVKEK NILLEVCPIS NVLLKNAKSM DTHPIRQLYD
AGVKVSVNSD DPGMFLTNIN DDYEELYTHL NFTLEDFMKM NEWALEKSFM DSNIKDKIKN
LYF
