PNPH_PLAFA
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 03-AUG-2022, entry version 83.
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 2'-
CC deoxyguanosine as substrate (PubMed:11707439). kcat is 0.026 sec(-1)
CC 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; MSDVFHL; -.
DR BioCyc; MetaCyc:MON-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 Gene3D; 3.40.50.1580; -; 1.
DR InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR Pfam; PF01048; PNP_UDP_1; 1.
DR SUPFAM; SSF53167; SSF53167; 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
