PURA_PLAFA
ID PURA_PLAFA Reviewed; 442 AA.
AC Q9U8D3;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Adenylosuccinate synthetase {ECO:0000255|HAMAP-Rule:MF_03125};
DE Short=AMPSase {ECO:0000255|HAMAP-Rule:MF_03125};
DE Short=AdSS {ECO:0000255|HAMAP-Rule:MF_03125};
DE EC=6.3.4.4 {ECO:0000255|HAMAP-Rule:MF_03125};
DE AltName: Full=IMP--aspartate ligase {ECO:0000255|HAMAP-Rule:MF_03125};
GN Name=Adss;
OS Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=T9/106;
RX PubMed=12071700; DOI=10.1006/prep.2001.1610;
RA Jayalakshmi R., Sumathy K., Balaram H.;
RT "Purification and characterization of recombinant Plasmodium falciparum
RT adenylosuccinate synthetase expressed in Escherichia coli.";
RL Protein Expr. Purif. 25:65-72(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-442, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, AND ACTIVITY REGULATION.
RC STRAIN=T9/106;
RA Sumathy K., Jayalakshmi R., Shivayogi M.S., Balaram H.;
RT "Cloning and characterization of the Plasmodium falciparum adenylosuccinate
RT synthetase gene.";
RL Curr. Sci. 78:101-105(2000).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=T9/106;
RX PubMed=15500910; DOI=10.1016/j.molbiopara.2004.06.013;
RA Raman J., Mehrotra S., Anand R.P., Balaram H.;
RT "Unique kinetic mechanism of Plasmodium falciparum adenylosuccinate
RT synthetase.";
RL Mol. Biochem. Parasitol. 138:1-8(2004).
RN [4]
RP FUNCTION.
RX PubMed=20654742; DOI=10.1016/j.bbapap.2010.07.015;
RA Mehrotra S., Mylarappa B.N., Iyengar P., Balaram H.;
RT "Studies on active site mutants of P. falciparum adenylosuccinate
RT synthetase: Insights into enzyme catalysis and activation.";
RL Biochim. Biophys. Acta 1804:1996-2002(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3-442 IN COMPLEX WITH IMP; GDP;
RP MAGNESIUM AND SUBSTRATE ANALOG.
RC STRAIN=T9/106;
RX PubMed=14729341; DOI=10.1016/j.jmb.2003.11.036;
RA Eaazhisai K., Jayalakshmi R., Gayathri P., Anand R.P., Sumathy K.,
RA Balaram H., Murthy M.R.;
RT "Crystal structure of fully ligated adenylosuccinate synthetase from
RT Plasmodium falciparum.";
RL J. Mol. Biol. 335:1251-1264(2004).
CC -!- FUNCTION: Plays an important role in the salvage pathway for purine
CC nucleotide biosynthesis. Catalyzes the first committed step in the
CC biosynthesis of AMP from IMP (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:12071700, ECO:0000269|PubMed:15500910,
CC ECO:0000269|PubMed:20654742}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + IMP + L-aspartate = GDP + 2 H(+) + N(6)-(1,2-
CC dicarboxyethyl)-AMP + phosphate; Xref=Rhea:RHEA:15753,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29991, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57567, ChEBI:CHEBI:58053,
CC ChEBI:CHEBI:58189; EC=6.3.4.4; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03125};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03125};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03125};
CC -!- ACTIVITY REGULATION: Inhibited by hadacidin. Activated by fructose 1,6-
CC bisphosphate. {ECO:0000269|PubMed:15500910, ECO:0000269|Ref.2}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18.4 uM for GTP {ECO:0000269|PubMed:15500910, ECO:0000269|Ref.2};
CC KM=23 uM for IMP {ECO:0000269|PubMed:15500910, ECO:0000269|Ref.2};
CC KM=1800 uM for L-aspartate {ECO:0000269|PubMed:15500910,
CC ECO:0000269|Ref.2};
CC pH dependence:
CC Optimum pH is 6.8-7.5. {ECO:0000269|PubMed:15500910,
CC ECO:0000269|Ref.2};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via de novo pathway; AMP
CC from IMP: step 1/2. {ECO:0000255|HAMAP-Rule:MF_03125}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03125}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03125}.
CC -!- MISCELLANEOUS: Parasitic protozoa lack the de novo purine biosynthesis
CC pathway and rely exclusively on the salvage pathway for their purine
CC nucleotide requirements.
CC -!- SIMILARITY: Belongs to the adenylosuccinate synthetase family.
CC {ECO:0000255|HAMAP-Rule:MF_03125}.
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DR EMBL; AF095282; AAF06822.2; -; mRNA.
DR PDB; 1P9B; X-ray; 2.00 A; A=3-442.
DR PDBsum; 1P9B; -.
DR AlphaFoldDB; Q9U8D3; -.
DR SMR; Q9U8D3; -.
DR DrugBank; DB03510; 6-O-Phosphoryl Inosine Monophosphate.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR DrugBank; DB02109; Hadacidin.
DR VEuPathDB; PlasmoDB:PF3D7_1354500; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000457000; -.
DR VEuPathDB; PlasmoDB:Pf7G8_130059100; -.
DR VEuPathDB; PlasmoDB:PfCD01_130060200; -.
DR VEuPathDB; PlasmoDB:PfDd2_130060400; -.
DR VEuPathDB; PlasmoDB:PfGA01_130060700; -.
DR VEuPathDB; PlasmoDB:PfGB4_130060500; -.
DR VEuPathDB; PlasmoDB:PfGN01_130061300; -.
DR VEuPathDB; PlasmoDB:PfHB3_130061000; -.
DR VEuPathDB; PlasmoDB:PfIT_130059900; -.
DR VEuPathDB; PlasmoDB:PfKE01_130060200; -.
DR VEuPathDB; PlasmoDB:PfKH01_130058600; -.
DR VEuPathDB; PlasmoDB:PfKH02_130057500; -.
DR VEuPathDB; PlasmoDB:PfML01_130058700; -.
DR VEuPathDB; PlasmoDB:PfNF135_130058800; -.
DR VEuPathDB; PlasmoDB:PfNF166_130059500; -.
DR VEuPathDB; PlasmoDB:PfNF54_130059200; -.
DR VEuPathDB; PlasmoDB:PfSD01_130061300; -.
DR VEuPathDB; PlasmoDB:PfSN01_130057600; -.
DR VEuPathDB; PlasmoDB:PfTG01_130060300; -.
DR BRENDA; 6.3.4.4; 4889.
DR UniPathway; UPA00075; UER00335.
DR EvolutionaryTrace; Q9U8D3; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004019; F:adenylosuccinate synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd03108; AdSS; 1.
DR Gene3D; 1.10.300.10; -; 1.
DR Gene3D; 3.40.440.10; -; 1.
DR Gene3D; 3.90.170.10; -; 1.
DR HAMAP; MF_00011; Adenylosucc_synth; 1.
DR InterPro; IPR018220; Adenylosuccin_syn_GTP-bd.
DR InterPro; IPR033128; Adenylosuccin_syn_Lys_AS.
DR InterPro; IPR042109; Adenylosuccinate_synth_dom1.
DR InterPro; IPR042110; Adenylosuccinate_synth_dom2.
DR InterPro; IPR042111; Adenylosuccinate_synth_dom3.
DR InterPro; IPR001114; Adenylosuccinate_synthetase.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11846; PTHR11846; 1.
DR Pfam; PF00709; Adenylsucc_synt; 1.
DR SMART; SM00788; Adenylsucc_synt; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00184; purA; 1.
DR PROSITE; PS01266; ADENYLOSUCCIN_SYN_1; 1.
DR PROSITE; PS00513; ADENYLOSUCCIN_SYN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; GTP-binding; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Purine biosynthesis.
FT CHAIN 1..442
FT /note="Adenylosuccinate synthetase"
FT /id="PRO_0000399294"
FT ACT_SITE 26
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT ACT_SITE 54
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 25..31
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 26..29
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 26
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 51..54
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 53..55
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 53
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 62
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 141
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 155
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 232
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 247
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 307..313
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 307
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 311
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 313
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 339..341
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT BINDING 425..427
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03125"
FT STRAND 16..25
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 29..36
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:1P9B"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 89..99
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 118..133
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 145..153
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 160..164
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 166..183
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 191..205
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 212..221
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:1P9B"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 253..258
FT /evidence="ECO:0007829|PDB:1P9B"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 269..280
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 293..301
FT /evidence="ECO:0007829|PDB:1P9B"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 320..330
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 340..343
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 347..357
FT /evidence="ECO:0007829|PDB:1P9B"
FT TURN 358..360
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 373..376
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 379..387
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:1P9B"
FT HELIX 404..417
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:1P9B"
FT STRAND 433..435
FT /evidence="ECO:0007829|PDB:1P9B"
SQ SEQUENCE 442 AA; 50065 MW; E20F5E1D36B34C4E CRC64;
MNIFDHQIKN VDKGNVVAIL GAQWGDEGKG KIIDMLSEYS DITCRFNGGA NAGHTISVND
KKYALHLLPC GVLYDNNISV LGNGMVIHVK SLMEEIESVG GKLLDRLYLS NKAHILFDIH
QIIDSIQETK KLKEGKQIGT TKRGIGPCYS TKASRIGIRL GTLKNFENFK NMYSKLIDHL
MDLYNITEYD KEKELNLFYN YHIKLRDRIV DVISFMNTNL ENNKKVLIEG ANAAMLDIDF
GTYPYVTSSC TTVGGVFSGL GIHHKKLNLV VGVVKSYLTR VGCGPFLTEL NNDVGQYLRE
KGHEYGTTTK RPRRCGWLDI PMLLYVKCIN SIDMINLTKL DVLSGLEEIL LCVNFKNKKT
GELLEKGCYP VEEEISEEYE PVYEKFSGWK EDISTCNEFD ELPENAKKYI LAIEKYLKTP
IVWIGVGPNR KNMIVKKNFN LN
