ADA_PLACD
ID ADA_PLACD Reviewed; 363 AA.
AC K6UCV4;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 1.
DT 03-AUG-2022, entry version 28.
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=PCYB_062380 {ECO:0000312|EMBL:GAB65506.1};
OS Plasmodium cynomolgi (strain B).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=1120755;
RN [1] {ECO:0000312|Proteomes:UP000006319}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=B {ECO:0000312|Proteomes:UP000006319};
RX PubMed=22863735; DOI=10.1038/ng.2375;
RA Tachibana S., Sullivan S.A., Kawai S., Nakamura S., Kim H.R., Goto N.,
RA Arisue N., Palacpac N.M.Q., Honma H., Yagi M., Tougan T., Katakai Y.,
RA Kaneko O., Mita T., Kita K., Yasutomi Y., Sutton P.L., Shakhbatyan R.,
RA Horii T., Yasunaga T., Barnwell J.W., Escalante A.A., Carlton J.M.,
RA Tanabe K.;
RT "Plasmodium cynomolgi genome sequences provide insight into Plasmodium
RT vivax and the monkey malaria clade.";
RL Nat. Genet. 44:1051-1055(2012).
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=87 uM for adenosine (at pH 8) {ECO:0000269|PubMed:19728741};
CC KM=8.7 uM for 5'-methylthioadenosine (MTA) (at pH 8)
CC {ECO:0000269|PubMed:19728741};
CC Note=kcat is 5.3 sec(-1) with adenosine as substrate
CC (PubMed:19728741). kcat is 0.31 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; DF157098; GAB65506.1; -; Genomic_DNA.
DR RefSeq; XP_004221453.1; XM_004221405.1.
DR AlphaFoldDB; K6UCV4; -.
DR SMR; K6UCV4; -.
DR STRING; 5827.XP_004221453.1; -.
DR EnsemblProtists; GAB65506; GAB65506; PCYB_062380.
DR GeneID; 14691746; -.
DR KEGG; pcy:PCYB_062380; -.
DR VEuPathDB; PlasmoDB:PCYB_062380; -.
DR eggNOG; KOG1097; Eukaryota.
DR PhylomeDB; K6UCV4; -.
DR UniPathway; UPA00606; -.
DR Proteomes; UP000006319; Chromosome 6.
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_0000451868"
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; 41956 MW; E645736A256BD07F CRC64;
MNILQEPIDF LKKDEIKNID LSQMSKKERY KIWKRIPKCE LHCHLDLCFS ADFFLSCIRK
YNLQPNLSDE EVLDYYLFAK GGKSLGEFVE KAIRVADIFH DYEVIEDLAK HAVFNKYKEG
VVLMEFRYSP TFVAFKYKLD IELIHQAIVK GIKEVVELLD HKIHVALMCI GDTGHEAANI
KASADFCLKH RADFVGFDHG GHEVDLKQYK EIFDYVRESG IPLSVHAGED VTLPNLNTLY
SAIQVLKVER IGHGIRVSES QELIDMVKEK NILLEVCPIS NVLLKNAKSM DTHPIRQLYD
AGVKVSVNSD DPGMFLTNIN DDYEELYTHL NFTLEDFMKM NEWALEKSFM DSNIKDKVKN
LYF
