ADA_PLAKN
ID ADA_PLAKN Reviewed; 363 AA.
AC A0A1Y3DYH2;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, 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:0000312|EMBL:OTN68356.1};
GN ORFNames=PKNOH_S03329100 {ECO:0000312|EMBL:OTN68356.1};
OS Plasmodium knowlesi.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5850 {ECO:0000312|Proteomes:UP000195012};
RN [1] {ECO:0000312|Proteomes:UP000195012}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Malayan Strain Pk1 (A+) {ECO:0000312|Proteomes:UP000195012};
RA Lapp S.A., Geraldo J.A., Chien J.-T., Ay F., Pakala S.B., Batugedara G.,
RA Humphrey J.C., Debarry J.D., Le Roch K.G., Galinski M.R., Kissinger J.C.;
RT "PacBio assembly of a Plasmodium knowlesi genome sequence with Hi-C
RT correction and manual annotation of the SICAvar gene family.";
RL Submitted (MAY-2017) to the EMBL/GenBank/DDBJ databases.
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=120 uM for adenosine (at pH 8) {ECO:0000269|PubMed:19728741};
CC KM=22 uM for 5'-methylthioadenosine (MTA) (at pH 8)
CC {ECO:0000269|PubMed:19728741};
CC Note=kcat is 6.8 sec(-1) with adenosine as substrate
CC (PubMed:19728741). kcat is 0.51 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; NETL01000017; OTN68356.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1Y3DYH2; -.
DR SMR; A0A1Y3DYH2; -.
DR VEuPathDB; PlasmoDB:PKA1H_060019400; -.
DR VEuPathDB; PlasmoDB:PKNH_0614300; -.
DR VEuPathDB; PlasmoDB:PKNOH_S03329100; -.
DR eggNOG; KOG1097; Eukaryota.
DR OMA; NHFTIHA; -.
DR UniPathway; UPA00606; -.
DR Proteomes; UP000195012; 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 Hydrolase; Metal-binding; Purine salvage; Zinc.
FT CHAIN 1..363
FT /note="Adenosine deaminase"
FT /id="PRO_0000451867"
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; 41906 MW; 33BEABA53AE4347C CRC64;
MNILQEPIDF LKKDELKNID LSQMDKKERY KIWKRIPKCE LHCHLDLCFS ADFFLSCVRK
YNLQPNLSDE EVLDYYLFAK GGKSLGEFVE KAIRVADIFQ DYEMIEDLAK HAVFNKYKEG
VVLMEFRYSP TFVAFKHNLD IELIHQAIVK GIKEVVELLD HKIDVTLLCI GDTGHRAADI
KASADFCLKH KADFVGFDHG GHEVDLKPYK EIFDYVKEGG MHLTVHAGED VTLPNLNTLY
SAIQVLKVER IGHGIRVSES QELIDMVKEN NILLEVCPIS NVLLKNAKSF DTHPIRKLYD
AGVKVSVSSD DPGMFLTNIN DDYEKLYTHL HFTLEDFMKM NEWALEKSFI GCDIKEKIKK
LYF
