IUNH_LEIMA
ID IUNH_LEIMA Reviewed; 314 AA.
AC P83851; Q6QMH8;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Inosine-uridine preferring nucleoside hydrolase {ECO:0000303|PubMed:10409664};
DE Short=IU-NH {ECO:0000303|PubMed:10409664};
DE Short=IU-nucleoside hydrolase {ECO:0000303|PubMed:10409664};
DE EC=3.2.2.2 {ECO:0000269|PubMed:10409664};
DE EC=3.2.2.3 {ECO:0000269|PubMed:10409664};
DE AltName: Full=Non-specific nucleoside hydrolase {ECO:0000303|PubMed:10409664};
GN Name=NSNH;
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MHOM/SU/73/5ASKH {ECO:0000312|EMBL:AAS48367.1};
RA Banuls A.L., Hide M.;
RT "Isolation and sequencing of nonspecific nucleoside hydrolase (nsnh) from
RT Leishmania.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|PDB:1EZR}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, ACTIVITY
RP REGULATION, SUBUNIT, AND PATHWAY.
RX PubMed=10409664; DOI=10.1074/jbc.274.30.21114;
RA Shi W., Schramm V.L., Almo S.C.;
RT "Nucleoside hydrolase from Leishmania major. Cloning, expression, catalytic
RT properties, transition state inhibitors, and the 2.5-A crystal structure.";
RL J. Biol. Chem. 274:21114-21120(1999).
CC -!- FUNCTION: Catalyzes the hydrolysis of the N-glycosidic bond of all of
CC the commonly occurring purine and pyrimidine nucleosides into ribose
CC and the associated base, but has a preference for inosine and uridine
CC as substrates. Likely functions in purine salvage from the host, a
CC fundamental pathway since protozoan parasites such as L.major are
CC incapable of de novo purine biosynthesis.
CC {ECO:0000269|PubMed:10409664}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + inosine = D-ribose + hypoxanthine; Xref=Rhea:RHEA:16657,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17368, ChEBI:CHEBI:17596,
CC ChEBI:CHEBI:47013; EC=3.2.2.2;
CC Evidence={ECO:0000269|PubMed:10409664};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + uridine = D-ribose + uracil; Xref=Rhea:RHEA:15577,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16704, ChEBI:CHEBI:17568,
CC ChEBI:CHEBI:47013; EC=3.2.2.3;
CC Evidence={ECO:0000269|PubMed:10409664};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000305|PubMed:10409664};
CC -!- ACTIVITY REGULATION: Is potently inhibited by immucillin A and
CC immucillin ACAP, which are transition state inhibitors.
CC {ECO:0000269|PubMed:10409664}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=445 uM for inosine {ECO:0000269|PubMed:10409664};
CC KM=234 uM for uridine {ECO:0000269|PubMed:10409664};
CC KM=140 uM for guanosine {ECO:0000269|PubMed:10409664};
CC KM=185 uM for adenosine {ECO:0000269|PubMed:10409664};
CC KM=422 uM for cytidine {ECO:0000269|PubMed:10409664};
CC Note=kcat is 119 sec(-1) with inosine as substrate. kcat is 32 sec(-
CC 1) with uridine as substrate. kcat is 0.6 sec(-1) with guanosine as
CC substrate. kcat is 0.6 sec(-1) with adenosine as substrate. kcat is
CC 0.4 sec(-1) with cytidine as substrate.
CC {ECO:0000269|PubMed:10409664};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000305|PubMed:10409664}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10409664}.
CC -!- SIMILARITY: Belongs to the IUNH family. {ECO:0000305}.
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DR EMBL; AY533501; AAS48367.1; -; Genomic_DNA.
DR PDB; 1EZR; X-ray; 2.50 A; A/B/C/D=1-314.
DR PDBsum; 1EZR; -.
DR AlphaFoldDB; P83851; -.
DR SMR; P83851; -.
DR STRING; 5664.LmjF.18.1580; -.
DR VEuPathDB; TriTrypDB:LmjF.18.1580; -.
DR VEuPathDB; TriTrypDB:LMJLV39_180021500; -.
DR VEuPathDB; TriTrypDB:LMJSD75_180021700; -.
DR eggNOG; KOG2938; Eukaryota.
DR UniPathway; UPA00606; -.
DR EvolutionaryTrace; P83851; -.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0047724; F:inosine nucleosidase activity; IDA:UniProtKB.
DR GO; GO:0008477; F:purine nucleosidase activity; IDA:UniProtKB.
DR GO; GO:0045437; F:uridine nucleosidase activity; IDA:UniProtKB.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043101; P:purine-containing compound salvage; TAS:UniProtKB.
DR Gene3D; 3.90.245.10; -; 1.
DR InterPro; IPR015910; I/U_nuclsd_hydro_CS.
DR InterPro; IPR001910; Inosine/uridine_hydrolase_dom.
DR InterPro; IPR023186; IUNH.
DR InterPro; IPR036452; Ribo_hydro-like.
DR PANTHER; PTHR12304; PTHR12304; 1.
DR Pfam; PF01156; IU_nuc_hydro; 1.
DR SUPFAM; SSF53590; SSF53590; 1.
DR PROSITE; PS01247; IUNH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Glycosidase; Hydrolase; Metal-binding;
KW Nucleotide metabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..314
FT /note="Inosine-uridine preferring nucleoside hydrolase"
FT /id="PRO_0000206811"
FT ACT_SITE 240
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q27546"
FT BINDING 10
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 14
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 15
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 160
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 166
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT CONFLICT 196
FT /note="Q -> L (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="V -> A (in Ref. 2)"
FT /evidence="ECO:0000305"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 13..24
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 42..55
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 130..138
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 148..152
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 173..180
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 186..189
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 201..210
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 213..228
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 242..249
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:1EZR"
FT TURN 268..272
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:1EZR"
FT STRAND 287..294
FT /evidence="ECO:0007829|PDB:1EZR"
FT HELIX 296..310
FT /evidence="ECO:0007829|PDB:1EZR"
SQ SEQUENCE 314 AA; 34310 MW; 947D924C65FD0723 CRC64;
MPRKIILDCD PGIDDAVAIF LAHGNPEIEL LAITTVVGNQ SLEKVTQNAR LVADVAGIVG
VPVAAGCTKP LVRGVRNASH IHGETGMGNV SYPPEFKTKL DGRHAVQLII DLIMSHEPKT
ITLVPTGGLT NIAMAVRLEP RIVDRVKEVV LMGGGYHTGN ASPVAEFNVF IDPEAAHIVF
NESWNVTMVG LDLTHQALAT PAVQKRVREV GTKPAAFMLQ ILDFYTKVYE KEHDTYGKVH
DPCAVAYVID PTVMTTERVP VDIELNGALT TGMTVVDFRY PRPKNCRTQV AVKLDFDKFW
CLVIDALERI GDPQ
