PNPH_PLAF7
ID PNPH_PLAF7 Reviewed; 245 AA.
AC Q8I3X4;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Purine nucleoside phosphorylase {ECO:0000303|PubMed:18957439};
DE EC=2.4.2.1 {ECO:0000269|PubMed:14982926, ECO:0000269|PubMed:16131758, ECO:0000269|PubMed:18957439, ECO:0000269|PubMed:19575810, ECO:0000269|PubMed:24416224, ECO:0000269|PubMed:29440412};
DE AltName: Full=PfPNP {ECO:0000303|PubMed:18957439};
DE AltName: Full=S-methyl-5'-thioinosine phosphorylase {ECO:0000303|PubMed:14982926};
DE EC=2.4.2.44 {ECO:0000269|PubMed:14982926, ECO:0000269|PubMed:18957439, ECO:0000269|PubMed:24416224};
GN Name=PNP {ECO:0000303|PubMed:18957439};
GN ORFNames=PF3D7_0513300 {ECO:0000312|EMBL:CAD51497.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18957439; DOI=10.1074/jbc.m807218200;
RA Madrid D.C., Ting L.M., Waller K.L., Schramm V.L., Kim K.;
RT "Plasmodium falciparum purine nucleoside phosphorylase is critical for
RT viability of malaria parasites.";
RL J. Biol. Chem. 283:35899-35907(2008).
RN [4] {ECO:0007744|PDB:1NW4, ECO:0007744|PDB:1Q1G}
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 2-245 IN COMPLEX WITH PHOSPHATE
RP ANALOG AND INHIBITOR IMMUCILLIN-H, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=14982926; DOI=10.1074/jbc.c400068200;
RA Shi W., Ting L.M., Kicska G.A., Lewandowicz A., Tyler P.C., Evans G.B.,
RA Furneaux R.H., Kim K., Almo S.C., Schramm V.L.;
RT "Plasmodium falciparum purine nucleoside phosphorylase: crystal structures,
RT immucillin inhibitors, and dual catalytic function.";
RL J. Biol. Chem. 279:18103-18106(2004).
RN [5] {ECO:0007744|PDB:1SQ6, ECO:0007744|PDB:2BSX}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH INOSINE, FUNCTION,
RP CATALYTIC ACTIVITY, PATHWAY, AND SUBUNIT.
RX PubMed=16131758; DOI=10.1107/s0907444905020251;
RA Schnick C., Robien M.A., Brzozowski A.M., Dodson E.J., Murshudov G.N.,
RA Anderson L., Luft J.R., Mehlin C., Hol W.G., Brannigan J.A.,
RA Wilkinson A.J.;
RT "Structures of Plasmodium falciparum purine nucleoside phosphorylase
RT complexed with sulfate and its natural substrate inosine.";
RL Acta Crystallogr. D 61:1245-1254(2005).
RN [6] {ECO:0007744|PDB:3ENZ}
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) IN COMPLEX WITH HYPOXANTHINE; RIBOSE
RP AND PHOSPHATE ANALOG, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=19575810; DOI=10.1186/1472-6807-9-42;
RA Chaikuad A., Brady R.L.;
RT "Conservation of structure and activity in Plasmodium purine nucleoside
RT phosphorylases.";
RL BMC Struct. Biol. 9:42-42(2009).
RN [7] {ECO:0007744|PDB:3PHC}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-245 IN COMPLEX WITH IN COMPLEX
RP WITH PHOSPHATE AND INHIBITOR DADME-IMMUCILLIN-G, AND SUBUNIT.
RA Ho M., Edwards A.A., Almo S.C., Schramm V.L.;
RT "Crystal Structure of Plasmodium falciparum purine nucleoside phosphorylase
RT in complex with DADMe-ImmG.";
RL Submitted (NOV-2010) to the PDB data bank.
RN [8] {ECO:0007744|PDB:3FOW}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-245 OF MUTANT ILE-66; ILE-73
RP AND PHE-160 IN COMPLEX WITH INHIBITOR IMMUCILLIN-H AND PHOSPHATE, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP PATHWAY, ACTIVE SITE, AND MUTAGENESIS OF HIS-7; ARG-45; TYR-47; VAL-66;
RP VAL-73; TYR-160; MET-183 AND ASP-206.
RX PubMed=24416224; DOI=10.1371/journal.pone.0084384;
RA Donaldson T.M., Ting L.M., Zhan C., Shi W., Zheng R., Almo S.C., Kim K.;
RT "Structural determinants of the 5'-methylthioinosine specificity of
RT Plasmodium purine nucleoside phosphorylase.";
RL PLoS ONE 9:e84384-e84384(2014).
RN [9] {ECO:0007744|PDB:6AQS, ECO:0007744|PDB:6AQU}
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF MUTANT ASP-181 AND ILE-183 IN
RP COMPLEX WITH PHOSPHATE AND INHIBITOR DADME-IMMUCILIN G, FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP MUTAGENESIS OF VAL-181 AND MET-183.
RX PubMed=29440412; DOI=10.1073/pnas.1525670115;
RA Ducati R.G., Namanja-Magliano H.A., Harijan R.K., Fajardo J.E., Fiser A.,
RA Daily J.P., Schramm V.L.;
RT "Genetic resistance to purine nucleoside phosphorylase inhibition in
RT Plasmodium falciparum.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:2114-2119(2018).
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:18957439, PubMed:14982926, PubMed:16131758, PubMed:19575810,
CC PubMed:24416224, PubMed:29440412). Preferentially acts on inosine and
CC guanosine, and to a lesser extent on 2'-deoxyguanosine and guanosine
CC (PubMed:14982926, PubMed:16131758, PubMed:19575810). Also catalyzes the
CC phosphorylation of S-methyl-5'-thioinosine (MTI) to hypoxanthine; MTI
CC is produced by adenosine deaminase (ADA)-mediated breakdown of S-
CC methyl-5'-thioadenosine (MTA), a major by-product of polyamine
CC biosynthesis (PubMed:18957439, PubMed:14982926, PubMed:24416224).
CC Generates hypoxanthine from both the purine salvage pathway and from
CC polyamine metabolism which is required for nucleic acids synthesis
CC (PubMed:18957439, PubMed:14982926, PubMed:24416224). Has no activity
CC towards adenosine (By similarity). {ECO:0000250|UniProtKB:Q8T9Z7,
CC ECO:0000269|PubMed:14982926, ECO:0000269|PubMed:16131758,
CC ECO:0000269|PubMed:18957439, ECO:0000269|PubMed:19575810,
CC ECO:0000269|PubMed:24416224, ECO:0000269|PubMed:29440412}.
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:14982926, ECO:0000269|PubMed:16131758,
CC ECO:0000269|PubMed:18957439, ECO:0000269|PubMed:19575810,
CC ECO:0000269|PubMed:24416224, ECO:0000269|PubMed:29440412};
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:19575810};
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:19575810};
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:19575810};
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:0000269|PubMed:14982926, ECO:0000269|PubMed:18957439,
CC ECO:0000269|PubMed:24416224};
CC -!- ACTIVITY REGULATION: Inhibited by Immucillin-H and 5'-methylthio-
CC Immucillin-H (PubMed:14982926, PubMed:24416224). Inhibited by 5'-deaza-
CC 1'-aza-2c-deoxy-1'-(9-methylene)-Immucilin-G (DADMe-ImmG)
CC (PubMed:29440412). {ECO:0000269|PubMed:14982926,
CC ECO:0000269|PubMed:24416224, ECO:0000269|PubMed:29440412}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.7 uM for inosine (at 25 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:14982926, ECO:0000269|PubMed:19575810};
CC KM=11 uM for inosine (at pH 7.4) {ECO:0000269|PubMed:24416224};
CC KM=7.6 uM for inosine (at 25 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:29440412};
CC KM=2.2 uM for guanosine {ECO:0000269|PubMed:19575810};
CC KM=25.3 uM for 2'-deoxyinosine {ECO:0000269|PubMed:19575810};
CC KM=16.3 uM for 2'-deoxyguanosine {ECO:0000269|PubMed:19575810};
CC KM=16 uM for 5'-methylthioinosine (at 25 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:14982926};
CC KM=8.8 uM for 5'-methylthioinosine (at pH 7.4)
CC {ECO:0000269|PubMed:24416224};
CC Note=kcat is 1.7 sec(-1) with inosine as substrate (PubMed:14982926,
CC PubMed:24416224). kcat is 2.63 sec(-1) with inosine as substrate
CC (PubMed:29440412). kcat is 1.1 sec(-1) with guanosine as substrate
CC (PubMed:19575810). kcat is 1.5 sec(-1) with 2'-deoxyinosine as
CC substrate (PubMed:19575810). kcat is 1.1 sec(-1) with 2'-
CC deoxyguanosine as substrate (PubMed:19575810). kcat is 1.5 sec(-1)
CC with 5'-methylthioinosine as substrate (PubMed:14982926). kcat is
CC 0.83 sec(-1) with 5'-methylthioinosine as substrate
CC (PubMed:24416224). {ECO:0000269|PubMed:14982926,
CC ECO:0000269|PubMed:19575810, ECO:0000269|PubMed:24416224,
CC ECO:0000269|PubMed:29440412};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000269|PubMed:14982926, ECO:0000269|PubMed:16131758,
CC ECO:0000269|PubMed:18957439, ECO:0000269|PubMed:19575810,
CC ECO:0000269|PubMed:24416224, ECO:0000269|PubMed:29440412}.
CC -!- SUBUNIT: Homohexamer; trimer of homodimers.
CC {ECO:0000269|PubMed:16131758, ECO:0000305|PubMed:14982926,
CC ECO:0000305|PubMed:19575810, ECO:0000305|Ref.7}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage,
CC including in trophozoites (at protein level).
CC {ECO:0000269|PubMed:18957439}.
CC -!- DISRUPTION PHENOTYPE: Severe growth defect in host erythrocytes which
CC is rescued by the addition of exogenous purines (PubMed:18957439). Loss
CC of purine nucleoside phosphorylase activity (PubMed:18957439).
CC {ECO:0000269|PubMed:18957439}.
CC -!- SIMILARITY: Belongs to the PNP/MTAP phosphorylase family.
CC {ECO:0000305}.
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DR EMBL; AL844504; CAD51497.1; -; Genomic_DNA.
DR RefSeq; XP_001351690.1; XM_001351654.1.
DR PDB; 1NW4; X-ray; 2.20 A; A/B/C/D/E/F=2-245.
DR PDB; 1Q1G; X-ray; 2.02 A; A/B/C/D/E/F=2-245.
DR PDB; 1SQ6; X-ray; 2.40 A; A=1-245.
DR PDB; 2BSX; X-ray; 2.00 A; A=1-245.
DR PDB; 3ENZ; X-ray; 2.03 A; A/B/C/D/E/F=1-245.
DR PDB; 3FOW; X-ray; 2.80 A; A/B=2-245.
DR PDB; 3PHC; X-ray; 2.00 A; A/B/C/D/E/F=2-245.
DR PDB; 6AQS; X-ray; 1.57 A; A=1-245.
DR PDB; 6AQU; X-ray; 2.60 A; A/B=1-245.
DR PDBsum; 1NW4; -.
DR PDBsum; 1Q1G; -.
DR PDBsum; 1SQ6; -.
DR PDBsum; 2BSX; -.
DR PDBsum; 3ENZ; -.
DR PDBsum; 3FOW; -.
DR PDBsum; 3PHC; -.
DR PDBsum; 6AQS; -.
DR PDBsum; 6AQU; -.
DR AlphaFoldDB; Q8I3X4; -.
DR SMR; Q8I3X4; -.
DR IntAct; Q8I3X4; 1.
DR STRING; 5833.PFE0660c; -.
DR ChEMBL; CHEMBL4523389; -.
DR DrugBank; DB03881; (2S,3R,4S,5S)-3,4-Dihydroxy-2-[(methylsulfanyl)methyl]-5-(4-oxo-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)pyrrolidinium.
DR DrugBank; DB11638; Artenimol.
DR SwissPalm; Q8I3X4; -.
DR PRIDE; Q8I3X4; -.
DR EnsemblProtists; CAD51497; CAD51497; PF3D7_0513300.
DR GeneID; 812947; -.
DR KEGG; pfa:PF3D7_0513300; -.
DR VEuPathDB; PlasmoDB:PF3D7_0513300; -.
DR HOGENOM; CLU_068457_0_1_1; -.
DR InParanoid; Q8I3X4; -.
DR OMA; MSDVFHL; -.
DR PhylomeDB; Q8I3X4; -.
DR BRENDA; 2.4.2.1; 4889.
DR BRENDA; 2.4.2.3; 4889.
DR Reactome; R-PFA-73614; Pyrimidine salvage.
DR Reactome; R-PFA-73621; Pyrimidine catabolism.
DR SABIO-RK; Q8I3X4; -.
DR UniPathway; UPA00606; -.
DR EvolutionaryTrace; Q8I3X4; -.
DR Proteomes; UP000001450; Chromosome 5.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0047975; F:guanosine phosphorylase activity; IEA:RHEA.
DR GO; GO:0004731; F:purine-nucleoside phosphorylase activity; IDA:UniProtKB.
DR GO; GO:0017061; F:S-methyl-5-thioadenosine phosphorylase activity; IDA:UniProtKB.
DR GO; GO:0004850; F:uridine phosphorylase activity; IBA:GO_Central.
DR GO; GO:0006148; P:inosine catabolic process; IDA:UniProtKB.
DR GO; GO:0006195; P:purine nucleotide catabolic process; IDA:UniProtKB.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR GO; GO:0006218; P:uridine catabolic process; IBA:GO_Central.
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; Reference proteome;
KW Transferase.
FT CHAIN 1..245
FT /note="Purine nucleoside phosphorylase"
FT /id="PRO_0000451825"
FT ACT_SITE 206
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:24416224"
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:0000305|PubMed:24416224, ECO:0000305|Ref.7,
FT ECO:0007744|PDB:3FOW, ECO:0007744|PDB:3PHC"
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:24416224, ECO:0000269|Ref.7,
FT ECO:0000305|PubMed:14982926, ECO:0000305|PubMed:19575810,
FT ECO:0007744|PDB:1NW4, ECO:0007744|PDB:1Q1G,
FT ECO:0007744|PDB:3ENZ, ECO:0007744|PDB:3FOW,
FT ECO:0007744|PDB:3PHC"
FT BINDING 45
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:24416224, ECO:0000269|Ref.7,
FT ECO:0000305|PubMed:14982926, ECO:0000305|PubMed:19575810,
FT ECO:0007744|PDB:1NW4, ECO:0007744|PDB:1Q1G,
FT ECO:0007744|PDB:3ENZ, ECO:0007744|PDB:3FOW,
FT ECO:0007744|PDB:3PHC"
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:24416224,
FT ECO:0000269|PubMed:29440412, ECO:0000269|Ref.7,
FT ECO:0000305|PubMed:14982926, ECO:0000305|PubMed:19575810,
FT ECO:0007744|PDB:1NW4, ECO:0007744|PDB:1Q1G,
FT ECO:0007744|PDB:3ENZ, ECO:0007744|PDB:3FOW,
FT ECO:0007744|PDB:3PHC, ECO:0007744|PDB:6AQS,
FT ECO:0007744|PDB:6AQU"
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:0000269|PubMed:16131758,
FT ECO:0000305|PubMed:24416224, ECO:0000305|Ref.7,
FT ECO:0007744|PDB:2BSX, ECO:0007744|PDB:3FOW,
FT ECO:0007744|PDB:3PHC"
FT MUTAGEN 7
FT /note="H->A: Slight decrease in catalytic activity towards
FT inosine and 5'-methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 7
FT /note="H->F: 23-fold decrease in catalytic efficiency for
FT inosine as substrate. Slight decrease in catalytic
FT efficiency for 5'-methylthioinosine as substrate."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 7
FT /note="H->S: Slight decrease in catalytic activity towards
FT inosine. Slight increase in catalytic activity towards 5'-
FT methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 45
FT /note="R->A: 1300-fold decrease in catalytic efficiency for
FT inosine as substrate. Loss of catalytic activity towards
FT 5'-methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 47
FT /note="Y->A: 790-fold decrease in catalytic efficiency for
FT inosine as substrate. 4000-fold decrease in catalytic
FT efficiency for 5'-methylthioinosine as substrate."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 66
FT /note="V->A: No effect on catalytic activity towards
FT inosine. Slight increase in catalytic efficiency with 5'-
FT methylthioinosine as substrate."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 66
FT /note="V->F: 40-fold decrease in catalytic efficiency with
FT inosine as substrate. Loss of catalytic activity towards
FT 5'-methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 66
FT /note="V->I: No effect on catalytic activity towards
FT inosine or 5'-methylthioinosine; when associated with I-73.
FT 20-fold decrease in catalytic efficiency with 5'-
FT methylthioinosine as substrate and no effect on catalytic
FT activity towards inosine; when associated with F-160. 170-
FT fold decrease in catalytic efficiency with 5'-
FT methylthioinosine as substrate and no effect on catalytic
FT activity towards inosine; when associated with I-73 and F-
FT 160."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 66
FT /note="V->S: 8-fold decrease in catalytic efficiency with
FT inosine as substrate. Slight increase in catalytic
FT efficiency with 5'-methylthioinosine as substrate."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 73
FT /note="V->A: Slight decrease in catalytic efficiency with
FT inosine or 5'-methylthioinosine as substrates."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 73
FT /note="V->F: Loss of catalytic activity towards inosine and
FT 5'-methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 73
FT /note="V->I: No effect on catalytic activity towards
FT inosine or 5'-methylthioinosine; when associated with I-66.
FT 20-fold decrease in catalytic efficiency with 5'-
FT methylthioinosine as substrate and no effect on catalytic
FT activity towards inosine; when associated with F-160. 170-
FT fold decrease in catalytic efficiency with 5'-
FT methylthioinosine as substrate and no effect on catalytic
FT activity towards inosine; when associated with I-66 and F-
FT 160."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 73
FT /note="V->S: Slight decrease in catalytic efficiency with
FT inosine as substrate. 8500-fold decrease in catalytic
FT efficiency with 5'-methylthioinosine as substrate."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 160
FT /note="Y->A: 680-fold decrease in catalytic efficiency with
FT inosine as substrate. 200-fold decrease in catalytic
FT efficiency with 5'-methylthioinosine as substrate."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 160
FT /note="Y->F: No effect on catalytic activity towards
FT inosine. 14-fold decrease in catalytic efficiency with 5'-
FT methylthioinosine as substrate. 20-fold decrease in
FT catalytic efficiency with 5'-methylthioinosine as
FT substrate; when associated with I-66 or I-73. 170-fold
FT decrease in catalytic efficiency with 5'-methylthioinosine
FT as substrate and no effect on catalytic activity towards
FT inosine; when associated with I-66 and I-73."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 181
FT /note="V->D: 4-fold decrease in catalytic efficiency with
FT inosine as substrate. Reduced affinity for DADMe-ImmG
FT inhibitor."
FT /evidence="ECO:0000269|PubMed:29440412"
FT MUTAGEN 183
FT /note="M->A: 20-fold decrease in affinity for inosine. Loss
FT of catalytic activity towards 5'-methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT MUTAGEN 183
FT /note="M->L: 17300-fold decrease in catalytic efficiency
FT with inosine as substrate. Reduced affinity for DADMe-ImmG
FT inhibitor."
FT /evidence="ECO:0000269|PubMed:29440412"
FT MUTAGEN 206
FT /note="D->A: 200-fold decrease in catalytic efficiency with
FT inosine as substrate. Loss of catalytic activity towards
FT 5'-methylthioinosine."
FT /evidence="ECO:0000269|PubMed:24416224"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 17..23
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 25..32
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 35..44
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 68..79
FT /evidence="ECO:0007829|PDB:6AQS"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 85..95
FT /evidence="ECO:0007829|PDB:6AQS"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 105..116
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 117..121
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 132..144
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 170..175
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 185..194
FT /evidence="ECO:0007829|PDB:6AQS"
FT STRAND 198..207
FT /evidence="ECO:0007829|PDB:6AQS"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:2BSX"
FT HELIX 223..241
FT /evidence="ECO:0007829|PDB:6AQS"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:6AQS"
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
