ADA_PLABA
ID ADA_PLABA Reviewed; 363 AA.
AC A0A509ALD0;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 1.
DT 03-AUG-2022, entry version 14.
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};
GN ORFNames=PBANKA_0513600 {ECO:0000312|EMBL:VUC54548.1};
OS Plasmodium berghei (strain Anka).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5823 {ECO:0000312|Proteomes:UP000074855};
RN [1] {ECO:0000312|Proteomes:UP000074855}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ANKA {ECO:0000312|Proteomes:UP000074855};
RX PubMed=25359557; DOI=10.1186/s12915-014-0086-0;
RA Otto T.D., Bohme U., Jackson A.P., Hunt M., Franke-Fayard B.,
RA Hoeijmakers W.A., Religa A.A., Robertson L., Sanders M., Ogun S.A.,
RA Cunningham D., Erhart A., Billker O., Khan S.M., Stunnenberg H.G.,
RA Langhorne J., Holder A.A., Waters A.P., Newbold C.I., Pain A., Berriman M.,
RA Janse C.J.;
RT "A comprehensive evaluation of rodent malaria parasite genomes and gene
RT expression.";
RL BMC Biol. 12:86-86(2014).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PATHWAY.
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 (Probable). {ECO:0000269|PubMed:19728741,
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};
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:0000250|UniProtKB:A5KE01};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:A5KE01};
CC -!- ACTIVITY REGULATION: Inhibited by coformycin and methylthiocoformycin
CC (MT-coformycin). {ECO:0000269|PubMed:19728741}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=57 uM for adenosine (at pH 8) {ECO:0000269|PubMed:19728741};
CC KM=4.4 uM for 5'-methylthioadenosine (MTA) (at pH 8)
CC {ECO:0000269|PubMed:19728741};
CC Note=kcat is 4.7 sec(-1) with adenosine as substrate
CC (PubMed:19728741). kcat is 0.35 sec(-1) with 5'-methylthioadenosine
CC as substrate (PubMed:19728741). {ECO:0000269|PubMed:19728741};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000305|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; LK023120; VUC54548.1; -; Genomic_DNA.
DR RefSeq; XP_677043.1; XM_671951.1.
DR AlphaFoldDB; A0A509ALD0; -.
DR SMR; A0A509ALD0; -.
DR STRING; 5823.A0A509ALD0; -.
DR VEuPathDB; PlasmoDB:PBANKA_0513600; -.
DR OMA; NHFTIHA; -.
DR UniPathway; UPA00606; -.
DR Proteomes; UP000074855; Chromosome 5.
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 Hydrolase; Metal-binding; Purine salvage; Reference proteome; Zinc.
FT CHAIN 1..363
FT /note="Adenosine deaminase"
FT /id="PRO_0000451869"
FT REGION 170..184
FT /note="Gating helix loop; regulates binding affinity for
FT substrates and thus substrate selectivity"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 44..46
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 172
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 201
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 229
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 253
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 310
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
FT SITE 172
FT /note="Important for substrate specificity for S-methyl-5'-
FT thioadenosine"
FT /evidence="ECO:0000250|UniProtKB:A5KE01"
SQ SEQUENCE 363 AA; 41989 MW; 9C9D79379CE1B351 CRC64;
MEIPNEEIKF LKKEDIKNIN LNGMNKKERY EIWKKIPKVE LHCHLDLTFS GKFFLKWVRK
YNLQPNMTDD QVLDHYLFTK EGKSLAEFIR KAISVSDIYR DYDILEDLAK WAVIEKYKEG
VVLMEFRYSP TFVSSSHGLD IELIHKAFVK GIKNATEMLN NKIYVALICI SDTGHSAASI
KHSGDFAIKH KHDFVGFDHG GREIDLKDHK DVYHSVRNHG LHLTVHAGED ATLPNLNTLY
TAINILNVER IGHGIRVSES EELIELVKKN NILLEVCPIS NLLLNNVKSM DTHPIRKLFD
AGVKVSVNSD DPGMFLTDIN DNYEKLYIHL NFTLEEFMTM NNWALEKSFV NDDIKSKLKT
MYF
