PNPH_ANOGA
ID PNPH_ANOGA Reviewed; 353 AA.
AC A4Q998; A7UTZ1;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Purine nucleoside phosphorylase {ECO:0000303|PubMed:17918964};
DE EC=2.4.2.1 {ECO:0000269|PubMed:17918964};
DE AltName: Full=AgPNP {ECO:0000303|PubMed:17918964};
DE AltName: Full=Inosine phosphorylase {ECO:0000305};
DE AltName: Full=Inosine-guanosine phosphorylase {ECO:0000305};
GN Name=pnp {ECO:0000303|PubMed:17918964};
GN ORFNames=AgaP_AGAP005945 {ECO:0000312|EMBL:EDO63766.1};
OS Anopheles gambiae (African malaria mosquito).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Anophelinae; Anopheles.
OX NCBI_TaxID=7165 {ECO:0000312|EMBL:CAM84316.1};
RN [1] {ECO:0000312|EMBL:CAM84316.1, ECO:0007744|PDB:2P4S}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION OF ISOFORM 2, X-RAY
RP CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH PHOSPHATE AND INHIBITOR
RP DADME-IMMH, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=17918964; DOI=10.1021/bi7010256;
RA Taylor E.A., Rinaldo-Matthis A., Li L., Ghanem M., Hazleton K.Z.,
RA Cassera M.B., Almo S.C., Schramm V.L.;
RT "Anopheles gambiae purine nucleoside phosphorylase: catalysis, structure,
RT and inhibition.";
RL Biochemistry 46:12405-12415(2007).
RN [2] {ECO:0000312|Proteomes:UP000007062}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=PEST {ECO:0000312|Proteomes:UP000007062};
RX PubMed=12364791; DOI=10.1126/science.1076181;
RA Holt R.A., Subramanian G.M., Halpern A., Sutton G.G., Charlab R.,
RA Nusskern D.R., Wincker P., Clark A.G., Ribeiro J.M.C., Wides R.,
RA Salzberg S.L., Loftus B.J., Yandell M.D., Majoros W.H., Rusch D.B., Lai Z.,
RA Kraft C.L., Abril J.F., Anthouard V., Arensburger P., Atkinson P.W.,
RA Baden H., de Berardinis V., Baldwin D., Benes V., Biedler J., Blass C.,
RA Bolanos R., Boscus D., Barnstead M., Cai S., Center A., Chaturverdi K.,
RA Christophides G.K., Chrystal M.A.M., Clamp M., Cravchik A., Curwen V.,
RA Dana A., Delcher A., Dew I., Evans C.A., Flanigan M.,
RA Grundschober-Freimoser A., Friedli L., Gu Z., Guan P., Guigo R.,
RA Hillenmeyer M.E., Hladun S.L., Hogan J.R., Hong Y.S., Hoover J.,
RA Jaillon O., Ke Z., Kodira C.D., Kokoza E., Koutsos A., Letunic I.,
RA Levitsky A.A., Liang Y., Lin J.-J., Lobo N.F., Lopez J.R., Malek J.A.,
RA McIntosh T.C., Meister S., Miller J.R., Mobarry C., Mongin E., Murphy S.D.,
RA O'Brochta D.A., Pfannkoch C., Qi R., Regier M.A., Remington K., Shao H.,
RA Sharakhova M.V., Sitter C.D., Shetty J., Smith T.J., Strong R., Sun J.,
RA Thomasova D., Ton L.Q., Topalis P., Tu Z.J., Unger M.F., Walenz B.,
RA Wang A.H., Wang J., Wang M., Wang X., Woodford K.J., Wortman J.R., Wu M.,
RA Yao A., Zdobnov E.M., Zhang H., Zhao Q., Zhao S., Zhu S.C., Zhimulev I.,
RA Coluzzi M., della Torre A., Roth C.W., Louis C., Kalush F., Mural R.J.,
RA Myers E.W., Adams M.D., Smith H.O., Broder S., Gardner M.J., Fraser C.M.,
RA Birney E., Bork P., Brey P.T., Venter J.C., Weissenbach J., Kafatos F.C.,
RA Collins F.H., Hoffman S.L.;
RT "The genome sequence of the malaria mosquito Anopheles gambiae.";
RL Science 298:129-149(2002).
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:17918964). Preferentially acts on 2'-deoxyinosine and inosine,
CC and to a lesser extent on 2'-deoxyguanosine and guanosine
CC (PubMed:17918964). Has no activity towards adenosine or 2'-
CC deoxyadenosine (PubMed:17918964). {ECO:0000269|PubMed:17918964}.
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:17918964};
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:17918964};
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:17918964};
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:17918964};
CC -!- ACTIVITY REGULATION: Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-
CC methylene) immucillin-H (DADMe-ImmH). {ECO:0000269|PubMed:17918964}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=585 uM for inosine (at 25 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:17918964};
CC KM=187 uM for guanosine (at 25 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:17918964};
CC KM=190 uM for 2-deoxyinosine (at 25 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:17918964};
CC KM=50 uM for 2-deoxyguanosine (at 25 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:17918964};
CC Note=kcat is 41 sec(-1) with inosine as substrate (PubMed:17918964).
CC kcat is 1 sec(-1) with guanosine as substrate (PubMed:17918964). kcat
CC is 54 sec(-1) with 2-deoxyinosine as substrate (PubMed:17918964).
CC kcat is 5.4 sec(-1) with 2-deoxyguanosine as substrate
CC (PubMed:17918964). {ECO:0000269|PubMed:17918964};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000269|PubMed:17918964}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000305|PubMed:17918964}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000303|PubMed:17918964};
CC IsoId=A4Q998-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:17918964};
CC IsoId=A4Q998-2; Sequence=VSP_060865;
CC -!- SIMILARITY: Belongs to the PNP/MTAP phosphorylase family.
CC {ECO:0000305}.
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DR EMBL; AM690372; CAM84316.1; -; Genomic_DNA.
DR EMBL; AAAB01008960; EDO63766.1; -; Genomic_DNA.
DR RefSeq; XP_001688760.1; XM_001688708.1.
DR PDB; 2P4S; X-ray; 2.20 A; A/B/C=1-353.
DR PDBsum; 2P4S; -.
DR AlphaFoldDB; A4Q998; -.
DR SMR; A4Q998; -.
DR STRING; 7165.AGAP005945-PA; -.
DR PaxDb; A4Q998; -.
DR GeneID; 1276614; -.
DR KEGG; aga:AgaP_AGAP005945; -.
DR VEuPathDB; VectorBase:AGAP005945; -.
DR eggNOG; KOG3984; Eukaryota.
DR HOGENOM; CLU_054456_1_2_1; -.
DR InParanoid; A4Q998; -.
DR OrthoDB; 1078969at2759; -.
DR PhylomeDB; A4Q998; -.
DR BRENDA; 2.4.2.1; 358.
DR UniPathway; UPA00606; -.
DR EvolutionaryTrace; A4Q998; -.
DR Proteomes; UP000007062; Chromosome 2L.
DR ExpressionAtlas; A4Q998; differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004731; F:purine-nucleoside phosphorylase activity; IBA:GO_Central.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR CDD; cd09009; PNP-EcPNPII_like; 1.
DR Gene3D; 3.40.50.1580; -; 1.
DR InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR InterPro; IPR011270; Pur_Nuc_Pase_Ino/Guo-sp.
DR InterPro; IPR011268; Purine_phosphorylase.
DR PANTHER; PTHR11904; PTHR11904; 1.
DR Pfam; PF01048; PNP_UDP_1; 1.
DR SUPFAM; SSF53167; SSF53167; 1.
DR TIGRFAMs; TIGR01700; PNPH; 1.
DR TIGRFAMs; TIGR01697; PNPH-PUNA-XAPA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Glycosyltransferase; Purine salvage;
KW Reference proteome; Transferase.
FT CHAIN 1..353
FT /note="Purine nucleoside phosphorylase"
FT /id="PRO_0000451765"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT BINDING 129
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT BINDING 149..151
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT BINDING 181
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT BINDING 266
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000305|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT BINDING 285
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT BINDING 308
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000305|PubMed:17918964,
FT ECO:0007744|PDB:2P4S"
FT VAR_SEQ 1..68
FT /note="MSKFSYLQNGKASTNGVPHANGHHQQHQNGHSNGVARNGGTATDTLPVAYQQ
FT KAATSGPFHMPRTEHV -> M (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:17918964"
FT /id="VSP_060865"
FT HELIX 72..85
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 158..171
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 175..184
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 194..201
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 203..206
FT /evidence="ECO:0007829|PDB:2P4S"
FT TURN 218..220
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 233..245
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 252..259
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 268..276
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 281..286
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 287..295
FT /evidence="ECO:0007829|PDB:2P4S"
FT STRAND 299..309
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:2P4S"
FT HELIX 333..350
FT /evidence="ECO:0007829|PDB:2P4S"
SQ SEQUENCE 353 AA; 38754 MW; B867293B262123EC CRC64;
MSKFSYLQNG KASTNGVPHA NGHHQQHQNG HSNGVARNGG TATDTLPVAY QQKAATSGPF
HMPRTEHVGY TYDTLQEIAT YLLERTELRP KVGIICGSGL GTLAEQLTDV DSFDYETIPH
FPVSTVAGHV GRLVFGYLAG VPVMCMQGRF HHYEGYPLAK CAMPVRVMHL IGCTHLIATN
AAGGANPKYR VGDIMLIKDH INLMGFAGNN PLQGPNDERF GPRFFGMANT YDPKLNQQAK
VIARQIGIEN ELREGVYTCL GGPNFETVAE VKMLSMLGVD AIGMSTVHEI ITARHCGMTC
FAFSLITNMC TMSYEEEEEH CHDSIVGVGK NREKTLGEFV SRIVKHIHYE AKK
