ID   PNPH_PLAFA              Reviewed;         245 AA.
AC   Q8T9Z7;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   27-MAR-2024, entry version 87.
DE   RecName: Full=Purine nucleoside phosphorylase {ECO:0000303|PubMed:11707439};
DE            EC=2.4.2.1 {ECO:0000269|PubMed:11707439, ECO:0000269|PubMed:30602534};
DE   AltName: Full=S-methyl-5'-thioinosine phosphorylase {ECO:0000250|UniProtKB:Q8I3X4};
DE            EC=2.4.2.44 {ECO:0000250|UniProtKB:Q8I3X4};
GN   Name=PNP {ECO:0000312|EMBL:AAL74412.1};
OS   Plasmodium falciparum.
OC   Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX   NCBI_TaxID=5833 {ECO:0000312|EMBL:AAL74412.1};
RN   [1] {ECO:0000312|EMBL:AAL74412.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC   STRAIN=FCB {ECO:0000269|PubMed:11707439};
RX   PubMed=11707439; DOI=10.1074/jbc.m105905200;
RA   Kicska G.A., Tyler P.C., Evans G.B., Furneaux R.H., Kim K., Schramm V.L.;
RT   "Transition state analogue inhibitors of purine nucleoside phosphorylase
RT   from Plasmodium falciparum.";
RL   J. Biol. Chem. 277:3219-3225(2002).
RN   [2] {ECO:0007744|PDB:5ZNC, ECO:0007744|PDB:5ZNI}
RP   X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) IN COMPLEX WITH INHIBITORS QUININE
RP   AND MEFLOQUINE, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC   STRAIN=FCB {ECO:0000269|PubMed:30602534};
RX   PubMed=30602534; DOI=10.1126/scitranslmed.aau3174;
RA   Dziekan J.M., Yu H., Chen D., Dai L., Wirjanata G., Larsson A., Prabhu N.,
RA   Sobota R.M., Bozdech Z., Nordlund P.;
RT   "Identifying purine nucleoside phosphorylase as the target of quinine using
RT   cellular thermal shift assay.";
RL   Sci. Transl. Med. 11:0-0(2019).
CC   -!- FUNCTION: As part of the purine salvage pathway, catalyzes the
CC       phosphorolytic breakdown of the N-glycosidic bond in the beta-
CC       (deoxy)ribonucleoside molecules, with the formation of the
CC       corresponding free purine bases and pentose-1-phosphate
CC       (PubMed:11707439, PubMed:30602534). Preferentially acts on inosine and
CC       guanosine, and to a lesser extent on 2'-deoxyinosine and 2'-
CC       deoxyguanosine (PubMed:11707439). Also catalyzes the phosphorylation of
CC       S-methyl-5'-thioinosine (MTI) to hypoxanthine; MTI is produced by
CC       adenosine deaminase (ADA)-mediated breakdown of S-methyl-5'-
CC       thioadenosine (MTA), a major by-product of polyamine biosynthesis (By
CC       similarity). Generates hypoxanthine from both the purine salvage
CC       pathway and from polyamine metabolism which is required for nucleic
CC       acids synthesis (By similarity). Has no activity towards adenosine
CC       (PubMed:11707439). {ECO:0000250|UniProtKB:Q8I3X4,
CC       ECO:0000269|PubMed:11707439, ECO:0000269|PubMed:30602534}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=inosine + phosphate = alpha-D-ribose 1-phosphate +
CC         hypoxanthine; Xref=Rhea:RHEA:27646, ChEBI:CHEBI:17368,
CC         ChEBI:CHEBI:17596, ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC         Evidence={ECO:0000269|PubMed:11707439, ECO:0000269|PubMed:30602534};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=guanosine + phosphate = alpha-D-ribose 1-phosphate + guanine;
CC         Xref=Rhea:RHEA:13233, ChEBI:CHEBI:16235, ChEBI:CHEBI:16750,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC         Evidence={ECO:0000269|PubMed:11707439};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2'-deoxyguanosine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC         phosphate + guanine; Xref=Rhea:RHEA:27738, ChEBI:CHEBI:16235,
CC         ChEBI:CHEBI:17172, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1;
CC         Evidence={ECO:0000269|PubMed:11707439};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2'-deoxyinosine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC         phosphate + hypoxanthine; Xref=Rhea:RHEA:27750, ChEBI:CHEBI:17368,
CC         ChEBI:CHEBI:28997, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1;
CC         Evidence={ECO:0000269|PubMed:11707439};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=phosphate + S-methyl-5'-thioinosine = hypoxanthine + S-methyl-
CC         5-thio-alpha-D-ribose 1-phosphate; Xref=Rhea:RHEA:30643,
CC         ChEBI:CHEBI:17368, ChEBI:CHEBI:43474, ChEBI:CHEBI:48595,
CC         ChEBI:CHEBI:58533; EC=2.4.2.44;
CC         Evidence={ECO:0000250|UniProtKB:Q8I3X4};
CC   -!- ACTIVITY REGULATION: Inhibited by Immucillin-H (PubMed:11707439,
CC       PubMed:30602534). Inhibited by antimalaria drugs quinine and mefloquine
CC       (PubMed:30602534). {ECO:0000269|PubMed:11707439,
CC       ECO:0000269|PubMed:30602534}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5 uM for inosine {ECO:0000269|PubMed:11707439};
CC         KM=104 uM for 2'-deoxyinosine {ECO:0000269|PubMed:11707439};
CC         KM=9.7 uM for guanosine {ECO:0000269|PubMed:11707439};
CC         KM=69 uM for 2'-deoxyguanosine {ECO:0000269|PubMed:11707439};
CC         KM=85 uM for uridine {ECO:0000269|PubMed:11707439};
CC         Note=kcat is 0.34 sec(-1) with inosine as substrate
CC         (PubMed:11707439). kcat is 0.14 sec(-1) with guanosine as substrate
CC         (PubMed:11707439). kcat is 0.64 sec(-1) with 2'-deoxyinosine as
CC         substrate (PubMed:11707439). kcat is 0.2 sec(-1) with
CC         2'-deoxyguanosine as substrate (PubMed:11707439). kcat is 0.026
CC         sec(-1) with uridine as substrate (PubMed:11707439).
CC         {ECO:0000269|PubMed:11707439};
CC   -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC       {ECO:0000269|PubMed:11707439}.
CC   -!- SUBUNIT: Homohexamer; trimer of homodimers.
CC       {ECO:0000250|UniProtKB:Q8I3X4}.
CC   -!- SIMILARITY: Belongs to the PNP/MTAP phosphorylase family.
CC       {ECO:0000305}.
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DR   EMBL; AF426159; AAL74412.1; -; Genomic_DNA.
DR   PDB; 5ZNC; X-ray; 1.66 A; A=1-245.
DR   PDB; 5ZNI; X-ray; 2.30 A; A=1-245.
DR   PDBsum; 5ZNC; -.
DR   PDBsum; 5ZNI; -.
DR   AlphaFoldDB; Q8T9Z7; -.
DR   SMR; Q8T9Z7; -.
DR   BindingDB; Q8T9Z7; -.
DR   ChEMBL; CHEMBL5648; -.
DR   DrugCentral; Q8T9Z7; -.
DR   VEuPathDB; PlasmoDB:PF3D7_0513300; -.
DR   VEuPathDB; PlasmoDB:Pf7G8-2_000132500; -.
DR   VEuPathDB; PlasmoDB:Pf7G8_050018500; -.
DR   VEuPathDB; PlasmoDB:PfCD01_050019700; -.
DR   VEuPathDB; PlasmoDB:PfDd2_050018200; -.
DR   VEuPathDB; PlasmoDB:PfGA01_050017700; -.
DR   VEuPathDB; PlasmoDB:PfGB4_050019200; -.
DR   VEuPathDB; PlasmoDB:PfGN01_050018200; -.
DR   VEuPathDB; PlasmoDB:PfHB3_050018200; -.
DR   VEuPathDB; PlasmoDB:PfIT_050018400; -.
DR   VEuPathDB; PlasmoDB:PfKE01_050017700; -.
DR   VEuPathDB; PlasmoDB:PfKH01_050018600; -.
DR   VEuPathDB; PlasmoDB:PfKH02_050018800; -.
DR   VEuPathDB; PlasmoDB:PfML01_050018100; -.
DR   VEuPathDB; PlasmoDB:PfNF135_050018800; -.
DR   VEuPathDB; PlasmoDB:PfNF166_050018400; -.
DR   VEuPathDB; PlasmoDB:PfNF54_050017500; -.
DR   VEuPathDB; PlasmoDB:PfSD01_050018200; -.
DR   VEuPathDB; PlasmoDB:PfSN01_050018500; -.
DR   VEuPathDB; PlasmoDB:PfTG01_050018200; -.
DR   OMA; PQCLLCG; -.
DR   BioCyc; MetaCyc:MONOMER-16356; -.
DR   BRENDA; 2.4.2.1; 4889.
DR   UniPathway; UPA00606; -.
DR   GO; GO:0047975; F:guanosine phosphorylase activity; IEA:RHEA.
DR   GO; GO:0004731; F:purine-nucleoside phosphorylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR   CDD; cd17767; UP_EcUdp-like; 1.
DR   Gene3D; 3.40.50.1580; Nucleoside phosphorylase domain; 1.
DR   InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR   InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR   PANTHER; PTHR43691:SF11; FI09636P-RELATED; 1.
DR   PANTHER; PTHR43691; URIDINE PHOSPHORYLASE; 1.
DR   Pfam; PF01048; PNP_UDP_1; 1.
DR   SUPFAM; SSF53167; Purine and uridine phosphorylases; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Glycosyltransferase; Purine salvage; Transferase.
FT   CHAIN           1..245
FT                   /note="Purine nucleoside phosphorylase"
FT                   /id="PRO_0000451826"
FT   ACT_SITE        206
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I3X4"
FT   BINDING         7
FT                   /ligand="a purine D-ribonucleoside"
FT                   /ligand_id="ChEBI:CHEBI:142355"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I3X4"
FT   BINDING         23..27
FT                   /ligand="phosphate"
FT                   /ligand_id="ChEBI:CHEBI:43474"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000269|PubMed:30602534,
FT                   ECO:0007744|PDB:5ZNI"
FT   BINDING         45
FT                   /ligand="phosphate"
FT                   /ligand_id="ChEBI:CHEBI:43474"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I3X4"
FT   BINDING         88..91
FT                   /ligand="phosphate"
FT                   /ligand_id="ChEBI:CHEBI:43474"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000269|PubMed:30602534,
FT                   ECO:0007744|PDB:5ZNC, ECO:0007744|PDB:5ZNI"
FT   BINDING         183..184
FT                   /ligand="a purine D-ribonucleoside"
FT                   /ligand_id="ChEBI:CHEBI:142355"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:Q8I3X4"
FT   TURN            6..8
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           12..14
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          17..23
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           25..32
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          35..44
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          47..54
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          57..63
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           68..80
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          85..95
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   TURN            97..99
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          105..116
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           117..121
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           132..144
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          150..158
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          164..166
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           170..175
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          180..184
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           185..195
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   STRAND          198..205
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           209..214
FT                   /evidence="ECO:0007829|PDB:5ZNC"
FT   HELIX           223..242
FT                   /evidence="ECO:0007829|PDB:5ZNC"
SQ   SEQUENCE   245 AA;  26858 MW;  2159E9731C410A23 CRC64;
     MDNLLRHLKI SKEQITPVVL VVGDPGRVDK IKVVCDSYVD LAYNREYKSV ECHYKGQKFL
     CVSHGVGSAG CAVCFEELCQ NGAKVIIRAG SCGSLQPDLI KRGDICICNA AVREDRVSHL
     LIHGDFPAVG DFDVYDTLNK CAQELNVPVF NGISVSSDMY YPNKIIPSRL EDYSKANAAV
     VEMELATLMV IGTLRKVKTG GILIVDGCPF KWDEGDFDNN LVPHQLENMI KIALGACAKL
     ATKYA
//