ADA_PLAF7
ID ADA_PLAF7 Reviewed; 367 AA.
AC Q8IJA9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Adenosine deaminase {ECO:0000305};
DE EC=3.5.4.4 {ECO:0000269|PubMed:19728741, ECO:0000269|PubMed:31002765};
DE AltName: Full=S-methyl-5'-thioadenosine deaminase {ECO:0000305};
DE EC=3.5.4.31 {ECO:0000269|PubMed:19728741, ECO:0000269|PubMed:31002765};
GN Name=ADA {ECO:0000305};
GN ORFNames=PF3D7_1029600 {ECO:0000312|EMBL:CZT98552.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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).
RN [3] {ECO:0007744|PDB:6II7}
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF MUTANT GLN-27 AND ILE-227 IN
RP COMPLEX WITH ZINC; INOSINE AND HYPOXANTHINE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND MUTAGENESIS OF CYS-27; PHE-136;
RP THR-174; ASP-176; LEU-179 AND LEU-227.
RX PubMed=31002765; DOI=10.1016/j.abb.2019.04.002;
RA Jaruwat A., Riangrungroj P., Ubonprasert S., Sae-Ueng U., Kuaprasert B.,
RA Yuthavong Y., Leartsakulpanich U., Chitnumsub P.;
RT "Crystal structure of Plasmodium falciparum adenosine deaminase reveals a
RT novel binding pocket for inosine.";
RL Arch. Biochem. Biophys. 667:6-13(2019).
CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine to produce
CC inosine (PubMed:19728741, PubMed:31002765). Unlike mammalian adenosine
CC deaminases, also catalyzes the deamination of 5'-methylthioadenosine
CC (MTA), a by-product of polyamine biosynthesis, to produce 5'-
CC methylthioinosine (MTI) (PubMed:19728741, PubMed:31002765). Plays an
CC essential role in the purine salvage pathway which allows the parasite
CC to use host cell purines for the synthesis of nucleic acids (Probable).
CC {ECO:0000269|PubMed:19728741, ECO:0000269|PubMed:31002765,
CC ECO:0000305|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, ECO:0000269|PubMed:31002765};
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, ECO:0000269|PubMed:31002765};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:31002765};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:31002765};
CC -!- ACTIVITY REGULATION: Inhibited by coformycin and methylthiocoformycin
CC (MT-coformycin). {ECO:0000269|PubMed:19728741}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=17.84 uM for adenosine (at pH 8) {ECO:0000269|PubMed:31002765};
CC KM=88 uM for adenosine (at pH 8) {ECO:0000269|PubMed:19728741};
CC KM=30.6 uM for 5'-methylthioadenosine (MTA) (at pH 8)
CC {ECO:0000269|PubMed:31002765};
CC KM=115 uM for 5'-methylthioadenosine (MTA) (at pH 8)
CC {ECO:0000269|PubMed:19728741};
CC Note=kcat is 4.1 sec(-1) with adenosine as substrate
CC (PubMed:31002765). kcat is 5.6 sec(-1) with adenosine as substrate
CC (PubMed:19728741). kcat is 13.92 sec(-1) with 5'-methylthioadenosine
CC as substrate (PubMed:31002765). kcat is 5.8 sec(-1) with 5'-
CC methylthioadenosine as substrate (PubMed:19728741).
CC {ECO:0000269|PubMed:19728741, ECO:0000269|PubMed:31002765};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000305|PubMed:31002765}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Adenosine and AMP deaminases family. {ECO:0000305}.
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DR EMBL; LN999944; CZT98552.1; -; Genomic_DNA.
DR RefSeq; XP_001347573.1; XM_001347537.1.
DR PDB; 6II7; X-ray; 2.48 A; A=1-367.
DR PDBsum; 6II7; -.
DR AlphaFoldDB; Q8IJA9; -.
DR SMR; Q8IJA9; -.
DR IntAct; Q8IJA9; 1.
DR STRING; 5833.PF10_0289; -.
DR DrugBank; DB11638; Artenimol.
DR SwissPalm; Q8IJA9; -.
DR PRIDE; Q8IJA9; -.
DR EnsemblProtists; CZT98552; CZT98552; PF3D7_1029600.
DR GeneID; 810446; -.
DR KEGG; pfa:PF3D7_1029600; -.
DR VEuPathDB; PlasmoDB:PF3D7_1029600; -.
DR HOGENOM; CLU_039228_0_2_1; -.
DR InParanoid; Q8IJA9; -.
DR OMA; NHFTIHA; -.
DR PhylomeDB; Q8IJA9; -.
DR BRENDA; 3.5.4.4; 4889.
DR Reactome; R-PFA-74217; Purine salvage.
DR UniPathway; UPA00606; -.
DR Proteomes; UP000001450; Chromosome 10.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
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:0006154; P:adenosine catabolic process; IBA:GO_Central.
DR GO; GO:0043103; P:hypoxanthine salvage; IBA:GO_Central.
DR GO; GO:0046103; P:inosine biosynthetic process; IBA:GO_Central.
DR GO; GO:0060169; P:negative regulation of adenosine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0009168; P:purine ribonucleoside monophosphate biosynthetic process; IEA:InterPro.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR CDD; cd01320; ADA; 1.
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..367
FT /note="Adenosine deaminase"
FT /id="PRO_0000451864"
FT REGION 174..188
FT /note="Gating helix loop; regulates binding affinity for
FT substrates and thus substrate selectivity"
FT /evidence="ECO:0000269|PubMed:31002765"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:31002765,
FT ECO:0007744|PDB:6II7"
FT BINDING 48..50
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 48
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:31002765,
FT ECO:0007744|PDB:6II7"
FT BINDING 176
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 205
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000305|PubMed:31002765,
FT ECO:0007744|PDB:6II7"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:31002765,
FT ECO:0007744|PDB:6II7"
FT BINDING 233
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 257
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 314
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:31002765,
FT ECO:0007744|PDB:6II7"
FT SITE 176
FT /note="Important for substrate specificity for S-methyl-5'-
FT thioadenosine"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT MUTAGEN 27
FT /note="C->Q: No effect on catalytic activity towards
FT adenosine or 5'-methylthioadenosine; when associated with
FT I-227."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 136
FT /note="F->L: Severe decrease in catalytic activity towards
FT adenosine or 5'-methylthioadenosine."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 174
FT /note="T->A: Slight decrease in affinity for adenosine and
FT severe reduction in affinity for 5'-methylthioadenosine."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 174
FT /note="T->I: Slight increase in affinity for adenosine and
FT severe reduction in affinity for 5'-methylthioadenosine."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 176
FT /note="D->A: 7-fold reduction in affinity for adenosine and
FT 9-fold reduction in affinity for 5'-methylthioadenosine.
FT Reduces further catalytic efficiency with adenosine or 5'-
FT methylthioadenosine as substrates; when associated H-179."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 176
FT /note="D->M: Severe reduction in catalytic efficiency with
FT adenosine or 5'-methylthioadenosine as substrates."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 179
FT /note="L->H: No effect on catalytic activity. Reduces
FT further catalytic efficiency with adenosine or 5'-
FT methylthioadenosine as substrates; when associated A-176."
FT /evidence="ECO:0000269|PubMed:31002765"
FT MUTAGEN 227
FT /note="L->I: No effect on catalytic activity towards
FT adenosine or 5'-methylthioadenosine; when associated with
FT Q-27."
FT /evidence="ECO:0000269|PubMed:31002765"
FT HELIX 30..39
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 55..64
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 89..96
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 106..122
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 125..132
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:6II7"
FT TURN 139..142
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 145..162
FT /evidence="ECO:0007829|PDB:6II7"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 166..174
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 181..193
FT /evidence="ECO:0007829|PDB:6II7"
FT TURN 194..197
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 214..222
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 226..232
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 241..248
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 259..263
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 265..273
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 277..280
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 282..287
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 299..304
FT /evidence="ECO:0007829|PDB:6II7"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 323..334
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 338..350
FT /evidence="ECO:0007829|PDB:6II7"
FT HELIX 356..366
FT /evidence="ECO:0007829|PDB:6II7"
SQ SEQUENCE 367 AA; 42466 MW; A38B309F1D725919 CRC64;
MNCKNMDTSY EIINYLTKDE LDIDLSCMDK KERYKIWKRL PKCELHCHLD VCFSVDFFLN
VIRKYNIQPN MSDEEIIDYY LFSKPGKSLD EFVEKALRLT DIYIDYTVVE DLAKHAVFNK
YKEGVVLMEF RYSPSFMSFK HNLDKDLIHE AIVKGLNEAV ALLEYKIQVG LLCTGDGGLS
HERMKEAAEF CIKHKKDFVG YDHAGHEVDL KPFKDIFDNI REEGISLSVH AGEDVSIPNL
NSLYTAINLL HVKRIGHGIR VSESQELIDL VKEKDILLEV CPISNVLLNN VKSMDTHPIR
MLYDAGVKVS VNSDDPGMFL TNITDNYEEL YTHLNFTLAD FMKMNLWAVQ KSFVDPDIKN
KIISKYF
