PUR2_CRYNH
ID PUR2_CRYNH Reviewed; 802 AA.
AC J9VYP5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Bifunctional purine biosynthetic protein ADE5,7 {ECO:0000303|PubMed:34416230};
DE Includes:
DE RecName: Full=Phosphoribosylamine--glycine ligase {ECO:0000305};
DE EC=6.3.4.13 {ECO:0000269|PubMed:34416230};
DE AltName: Full=Glycinamide ribonucleotide synthetase {ECO:0000305};
DE Short=GAR synthetase {ECO:0000250|UniProtKB:P20772};
DE Short=GARS {ECO:0000305};
DE AltName: Full=Phosphoribosylglycinamide synthetase {ECO:0000305};
DE Includes:
DE RecName: Full=Phosphoribosylformylglycinamidine cyclo-ligase {ECO:0000305};
DE EC=6.3.3.1 {ECO:0000250|UniProtKB:P20772};
DE AltName: Full=AIR synthase {ECO:0000250|UniProtKB:P20772};
DE Short=AIR synthetase {ECO:0000250|UniProtKB:P20772};
DE Short=AIRS {ECO:0000305};
DE AltName: Full=Phosphoribosyl-aminoimidazole synthetase {ECO:0000305};
GN Name=ADE57 {ECO:0000250|UniProtKB:P07244};
GN Synonyms=ADE5,7 {ECO:0000303|PubMed:34416230};
GN ORFNames=CNAG_06314 {ECO:0000312|EMBL:AFR98551.1};
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443 {ECO:0000312|Proteomes:UP000010091};
RN [1] {ECO:0000312|Proteomes:UP000010091}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487
RC {ECO:0000312|Proteomes:UP000010091};
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-452, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=34416230; DOI=10.1016/j.jbc.2021.101091;
RA Chua S.M.H., Wizrah M.S.I., Luo Z., Lim B.Y.J., Kappler U., Kobe B.,
RA Fraser J.A.;
RT "Structural features of Cryptococcus neoformans bifunctional GAR/AIR
RT synthetase may present novel antifungal drug targets.";
RL J. Biol. Chem. 297:101091-101091(2021).
CC -!- FUNCTION: Catalyzes the second and fifth step in the 'de novo' purine
CC biosynthesis pathway; contains phosphoribosylamine--glycine ligase
CC (GARS) and phosphoribosylformylglycinamidine cyclo-ligase (AIRS)
CC activities. {ECO:0000269|PubMed:34416230}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-formamido-N(1)-(5-O-phospho-beta-D-ribosyl)acetamidine + ATP
CC = 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:23032, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:137981,
CC ChEBI:CHEBI:147287, ChEBI:CHEBI:456216; EC=6.3.3.1;
CC Evidence={ECO:0000250|UniProtKB:P20772};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-phospho-beta-D-ribosylamine + ATP + glycine = ADP + H(+) +
CC N(1)-(5-phospho-beta-D-ribosyl)glycinamide + phosphate;
CC Xref=Rhea:RHEA:17453, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57305, ChEBI:CHEBI:58681,
CC ChEBI:CHEBI:143788, ChEBI:CHEBI:456216; EC=6.3.4.13;
CC Evidence={ECO:0000269|PubMed:34416230};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Note=Binds two magnesium or manganese ions per subunit. {ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=48 uM for ATP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:34416230};
CC KM=496 uM for glycine (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:34416230};
CC KM=131 uM for phosphoribosyl-amine (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:34416230};
CC Note=kcat is 27.3 sec(-1) for phosphoribosylamine--glycine ligase
CC activity (at 37 degrees Celsius). {ECO:0000269|PubMed:34416230};
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole from N(2)-formyl-N(1)-(5-
CC phospho-D-ribosyl)glycinamide: step 2/2. {ECO:0000305|PubMed:34416230}.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; N(1)-
CC (5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-
CC diphosphate: step 2/2. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:34416230}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P20772}.
CC -!- DISRUPTION PHENOTYPE: Growth auxotrophic for adenine (PubMed:34416230).
CC Avirulent in a mouse inhalation infection model (PubMed:34416230). Does
CC not appear to affect production of the virulence factors melanin,
CC protease, urease, or phospholipase B, or on capsule formation
CC (PubMed:34416230). {ECO:0000269|PubMed:34416230}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the GARS family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the AIR synthase
CC family. {ECO:0000305}.
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DR EMBL; CP003832; AFR98551.1; -; Genomic_DNA.
DR RefSeq; XP_012053406.1; XM_012198016.1.
DR PDB; 7LVO; X-ray; 2.00 A; A=1-452.
DR PDB; 7LVP; X-ray; 2.24 A; A=492-802.
DR PDBsum; 7LVO; -.
DR PDBsum; 7LVP; -.
DR SMR; J9VYP5; -.
DR SwissPalm; J9VYP5; -.
DR EnsemblFungi; AFR98551; AFR98551; CNAG_06314.
DR GeneID; 23889525; -.
DR VEuPathDB; FungiDB:CNAG_06314; -.
DR HOGENOM; CLU_005361_1_1_1; -.
DR UniPathway; UPA00074; UER00125.
DR UniPathway; UPA00074; UER00129.
DR Proteomes; UP000010091; Chromosome 13.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004637; F:phosphoribosylamine-glycine ligase activity; IDA:UniProtKB.
DR GO; GO:0004641; F:phosphoribosylformylglycinamidine cyclo-ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IEA:InterPro.
DR CDD; cd02196; PurM; 1.
DR Gene3D; 3.30.1330.10; -; 1.
DR Gene3D; 3.30.1490.20; -; 1.
DR Gene3D; 3.90.600.10; -; 1.
DR Gene3D; 3.90.650.10; -; 1.
DR HAMAP; MF_00741; AIRS; 1.
DR HAMAP; MF_00138; GARS; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR InterPro; IPR020561; PRibGlycinamid_synth_ATP-grasp.
DR InterPro; IPR000115; PRibGlycinamide_synth.
DR InterPro; IPR020560; PRibGlycinamide_synth_C-dom.
DR InterPro; IPR037123; PRibGlycinamide_synth_C_sf.
DR InterPro; IPR020559; PRibGlycinamide_synth_CS.
DR InterPro; IPR020562; PRibGlycinamide_synth_N.
DR InterPro; IPR010918; PurM-like_C_dom.
DR InterPro; IPR036676; PurM-like_C_sf.
DR InterPro; IPR016188; PurM-like_N.
DR InterPro; IPR036921; PurM-like_N_sf.
DR InterPro; IPR004733; PurM_cligase.
DR InterPro; IPR011054; Rudment_hybrid_motif.
DR PANTHER; PTHR10520; PTHR10520; 1.
DR Pfam; PF00586; AIRS; 1.
DR Pfam; PF02769; AIRS_C; 1.
DR Pfam; PF01071; GARS_A; 1.
DR Pfam; PF02843; GARS_C; 1.
DR Pfam; PF02844; GARS_N; 1.
DR SMART; SM01210; GARS_C; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR SUPFAM; SSF55326; SSF55326; 1.
DR SUPFAM; SSF56042; SSF56042; 1.
DR TIGRFAMs; TIGR00877; purD; 1.
DR TIGRFAMs; TIGR00878; purM; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS00184; GARS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Ligase; Magnesium; Manganese;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Purine biosynthesis.
FT CHAIN 1..802
FT /note="Bifunctional purine biosynthetic protein ADE5,7"
FT /id="PRO_0000454643"
FT DOMAIN 126..339
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT REGION 1..444
FT /note="GARS"
FT /evidence="ECO:0000255"
FT REGION 455..788
FT /note="AIRS"
FT /evidence="ECO:0000255"
FT BINDING 157..218
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 307
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 309
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT STRAND 12..20
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 23..32
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 38..45
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 48..53
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:7LVO"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 71..80
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 90..94
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 97..102
FT /evidence="ECO:0007829|PDB:7LVO"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:7LVO"
FT TURN 113..116
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 122..131
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 183..194
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 216..226
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:7LVO"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 263..272
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 274..283
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 289..299
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 302..309
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 316..320
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 330..338
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 351..360
FT /evidence="ECO:0007829|PDB:7LVO"
FT TURN 362..365
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 383..392
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:7LVO"
FT STRAND 401..413
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 414..425
FT /evidence="ECO:0007829|PDB:7LVO"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:7LVO"
FT TURN 499..503
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 505..515
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 518..526
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 530..545
FT /evidence="ECO:0007829|PDB:7LVP"
FT TURN 546..548
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 550..555
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 566..582
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 606..614
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 615..617
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 629..634
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 636..638
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 643..652
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 669..674
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 681..689
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 694..698
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 703..707
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 708..711
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 719..723
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 731..739
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 744..747
FT /evidence="ECO:0007829|PDB:7LVP"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 755..761
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 763..765
FT /evidence="ECO:0007829|PDB:7LVP"
FT HELIX 766..775
FT /evidence="ECO:0007829|PDB:7LVP"
FT STRAND 780..795
FT /evidence="ECO:0007829|PDB:7LVP"
FT TURN 797..801
FT /evidence="ECO:0007829|PDB:7LVP"
SQ SEQUENCE 802 AA; 84591 MW; 4EEA42E456B04D98 CRC64;
MPEITAFPQP KSDLSILLLG AGGREHALAF KLAQSSRVAR IVVCPGNGGT ALMGGKVSNL
ALPWGAPPAF RSIVEWAQKE NIDLVVPGPE QPLVDGVEGA FKKVGIPVFG PSPAAAMLEG
SKSLSKEFMA RHNIPTAAFR SFTSTQYEDA VAYIKSKPFT SGRSVIKASG LAAGKGVLIP
ETDEEAFAAL KSVMVDKEFG DAGDEVVVEE YLSGPEISVL AFSDGYTIVP MPAAQDHKRI
GEGDTGLNTG GMGAYAPAPI ATKEIMERCV KDVLEPTIKG MREDGYPFVG MLFTGFMITA
DGPRVLEYNV RFGDPETQAL MLLLDEQTDL AEVLLACVER RLDSIKLGYK QGYAVSVVLA
SEGYPGSYPK GLPMTLNPTP EGVEVFHAGT KRSDNVTVTD GGRVLAVCAS APTLRAAVDL
AYSGISQISF QGQTFRRDIA YRALSSEPPA EPKGLTYAAA GVSVDAGNDL VEAIKPVVKA
TRRPGADSDI GGFGGAFDLA KAGYKDPILV SGTDGVGTKL RVALDHGKHN TVGIDLVAMS
VNDLIVQGAE PLYFLDYYAC SKLDVPVAAD VITGIAEGCL QAGCALIGGE TAEMPGMYHG
DDYDLAGFAV GVVERAQILP TPDIASGDVL LALSSSGPHS NGFSLIRKIV SLSNLSLHDT
APWDKNTSVG DALLTPTKVY IKPLLPGIKS GLYKGMSHIT GGGFTENIPR IFSSASNLGV
KLDLTSYSLP AIWKWLMRAG NVEAKEMVRT FNCGVGMIII VAKDKADAAL SSLKENGEEA
WVIGEVQEKK GVEYVGLDKF GL
