ID PUR8_BACSU Reviewed; 431 AA.
AC P12047;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 27-MAR-2024, entry version 169.
DE RecName: Full=Adenylosuccinate lyase;
DE Short=ASL;
DE EC=4.3.2.2 {ECO:0000269|PubMed:15182182};
DE AltName: Full=Adenylosuccinase;
DE Short=ASase;
DE AltName: Full=Glutamyl--tRNA ligase regulatory factor;
GN Name=purB; Synonyms=purE; OrderedLocusNames=BSU06440;
OS Bacillus subtilis (strain 168).
OC Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3036807; DOI=10.1016/s0021-9258(18)47560-6;
RA Ebbole D.J., Zalkin H.;
RT "Cloning and characterization of a 12-gene cluster from Bacillus subtilis
RT encoding nine enzymes for de novo purine nucleotide synthesis.";
RL J. Biol. Chem. 262:8274-8287(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [3]
RP PROTEIN SEQUENCE OF 1-30.
RC STRAIN=168 / BGSC1A1;
RX PubMed=1608947; DOI=10.1073/pnas.89.12.5389;
RA Gendron N., Breton R., Champagne N., Lapointe J.;
RT "Adenylosuccinate lyase of Bacillus subtilis regulates the activity of the
RT glutamyl-tRNA synthetase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5389-5392(1992).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF HIS-89; HIS-141;
RP GLN-212; ASN-270 AND ARG-301.
RX PubMed=15182182; DOI=10.1021/bi0494774;
RA Segall M.L., Colman R.F.;
RT "Gln212, Asn270, and Arg301 are critical for catalysis by adenylosuccinate
RT lyase from Bacillus subtilis.";
RL Biochemistry 43:7391-7402(2004).
RN [5]
RP SUBUNIT.
RX PubMed=18237141; DOI=10.1021/bi701400c;
RA De Zoysa Ariyananda L., Colman R.F.;
RT "Evaluation of types of interactions in subunit association in Bacillus
RT subtilis adenylosuccinate lyase.";
RL Biochemistry 47:2923-2934(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS).
RX PubMed=10926519; DOI=10.1006/jmbi.2000.3970;
RA Toth E.A., Worby C., Dixon J.E., Goedken E.R., Marqusee S., Yeates T.O.;
RT "The crystal structure of adenylosuccinate lyase from Pyrobaculum
RT aerophilum reveals an intracellular protein with three disulfide bonds.";
RL J. Mol. Biol. 301:433-450(2000).
CC -!- FUNCTION: Catalyzes two reactions in de novo purine nucleotide
CC biosynthesis. Catalyzes the breakdown of 5-aminoimidazole- (N-
CC succinylocarboxamide) ribotide (SAICAR or 2-[5-amino-1-(5-phospho-beta-
CC D-ribosyl)imidazole-4-carboxamido]succinate) to 5-aminoimidazole-4-
CC carboxamide ribotide (AICAR or 5-amino-1-(5-phospho-beta-D-
CC ribosyl)imidazole-4-carboxamide) and fumarate, and of adenylosuccinate
CC (ADS or N(6)-(1,2-dicarboxyethyl)-AMP) to adenosine monophosphate (AMP)
CC and fumarate (PubMed:15182182). Influences the affinity of glutamyl--
CC tRNA ligase for its substrates and increases its thermostability.
CC {ECO:0000269|PubMed:15182182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-(1,2-dicarboxyethyl)-AMP = AMP + fumarate;
CC Xref=Rhea:RHEA:16853, ChEBI:CHEBI:29806, ChEBI:CHEBI:57567,
CC ChEBI:CHEBI:456215; EC=4.3.2.2;
CC Evidence={ECO:0000269|PubMed:15182182};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16854;
CC Evidence={ECO:0000305|PubMed:15182182};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
CC carboxamido]succinate = 5-amino-1-(5-phospho-beta-D-
CC ribosyl)imidazole-4-carboxamide + fumarate; Xref=Rhea:RHEA:23920,
CC ChEBI:CHEBI:29806, ChEBI:CHEBI:58443, ChEBI:CHEBI:58475; EC=4.3.2.2;
CC Evidence={ECO:0000269|PubMed:15182182};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23921;
CC Evidence={ECO:0000305|PubMed:15182182};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via de novo pathway; AMP
CC from IMP: step 2/2.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-
CC phospho-D-ribosyl)imidazole-4-carboxylate: step 2/2.
CC -!- SUBUNIT: Homotetramer. Residues from neighboring subunits contribute
CC catalytic and substrate-binding residues to each active site.
CC {ECO:0000269|PubMed:15182182, ECO:0000269|PubMed:18237141}.
CC -!- SIMILARITY: Belongs to the lyase 1 family. Adenylosuccinate lyase
CC subfamily. {ECO:0000305}.
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DR EMBL; J02732; AAA22676.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB12464.1; -; Genomic_DNA.
DR PIR; C29326; WZBSDS.
DR RefSeq; NP_388526.1; NC_000964.3.
DR RefSeq; WP_003233955.1; NZ_JNCM01000032.1.
DR PDB; 1F1O; X-ray; 3.25 A; A=1-431.
DR PDBsum; 1F1O; -.
DR AlphaFoldDB; P12047; -.
DR SMR; P12047; -.
DR IntAct; P12047; 3.
DR MINT; P12047; -.
DR STRING; 224308.BSU06440; -.
DR PaxDb; 224308-BSU06440; -.
DR EnsemblBacteria; CAB12464; CAB12464; BSU_06440.
DR GeneID; 83883906; -.
DR GeneID; 936048; -.
DR KEGG; bsu:BSU06440; -.
DR PATRIC; fig|224308.179.peg.700; -.
DR eggNOG; COG0015; Bacteria.
DR InParanoid; P12047; -.
DR OrthoDB; 9768878at2; -.
DR PhylomeDB; P12047; -.
DR BioCyc; BSUB:BSU06440-MONOMER; -.
DR BRENDA; 4.3.2.2; 658.
DR SABIO-RK; P12047; -.
DR UniPathway; UPA00074; UER00132.
DR UniPathway; UPA00075; UER00336.
DR EvolutionaryTrace; P12047; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070626; F:(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity; IBA:GO_Central.
DR GO; GO:0004018; F:N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity; IDA:MGI.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006167; P:AMP biosynthetic process; IDA:MGI.
DR CDD; cd01360; Adenylsuccinate_lyase_1; 1.
DR Gene3D; 1.10.40.30; Fumarase/aspartase (C-terminal domain); 1.
DR Gene3D; 1.20.200.10; Fumarase/aspartase (Central domain); 1.
DR Gene3D; 1.10.275.10; Fumarase/aspartase (N-terminal domain); 1.
DR InterPro; IPR019468; AdenyloSucc_lyase_C.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR020557; Fumarate_lyase_CS.
DR InterPro; IPR000362; Fumarate_lyase_fam.
DR InterPro; IPR022761; Fumarate_lyase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR InterPro; IPR004769; Pur_lyase.
DR NCBIfam; TIGR00928; purB; 1.
DR PANTHER; PTHR43172; ADENYLOSUCCINATE LYASE; 1.
DR PANTHER; PTHR43172:SF1; ADENYLOSUCCINATE LYASE; 1.
DR Pfam; PF10397; ADSL_C; 1.
DR Pfam; PF00206; Lyase_1; 1.
DR PRINTS; PR00145; ARGSUCLYASE.
DR PRINTS; PR00149; FUMRATELYASE.
DR SMART; SM00998; ADSL_C; 1.
DR SUPFAM; SSF48557; L-aspartase-like; 1.
DR PROSITE; PS00163; FUMARATE_LYASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Lyase; Purine biosynthesis;
KW Reference proteome.
FT CHAIN 1..431
FT /note="Adenylosuccinate lyase"
FT /id="PRO_0000137873"
FT ACT_SITE 141
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT ACT_SITE 262
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 4..5
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 67..69
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 93..94
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 212
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 263
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 268..270
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 276
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT BINDING 307..311
FT /ligand="N(6)-(1,2-dicarboxyethyl)-AMP"
FT /ligand_id="ChEBI:CHEBI:57567"
FT /evidence="ECO:0000250|UniProtKB:P0AB89"
FT MUTAGEN 89
FT /note="H->Q: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15182182"
FT MUTAGEN 141
FT /note="H->Q: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15182182"
FT MUTAGEN 212
FT /note="Q->E: Decreases catalytic activity 1000-fold."
FT /evidence="ECO:0000269|PubMed:15182182"
FT MUTAGEN 212
FT /note="Q->M: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15182182"
FT MUTAGEN 270
FT /note="N->D,L: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15182182"
FT MUTAGEN 301
FT /note="R->K,Q: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15182182"
FT CONFLICT 5
FT /note="Y -> K (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 431 AA; 49485 MW; 89D2ED7F7F6D46A2 CRC64;
MIERYSRPEM SAIWTDENRF QAWLEVEILA CEAWAELGVI PKEDVKVMRE NASFDINRIL
EIEKDTRHDV VAFTRAVSES LGEERKWVHY GLTSTDVVDT ALSYLLKQAN DILLKDLERF
VDIIKEKAKE HKYTVMMGRT HGVHAEPTTF GLKLALWHEE MKRNLERFKQ AKAGIEVGKI
SGAVGTYANI DPFVEQYVCE KLGLKAAPIS TQTLQRDRHA DYMATLALIA TSIEKFAVEI
RGLQKSETRE VEEFFAKGQK GSSAMPHKRN PIGSENMTGM ARVIRGYMMT AYENVPLWHE
RDISHSSAER IILPDATIAL NYMLNRFSNI VKNLTVFPEN MKRNMDRTLG LIYSQRVLLA
LIDTGLTREE AYDTVQPKAM EAWEKQVPFR ELVEAEEKIT SRLSPEKIAD CFDYNYHLKN
VDLIFERLGL A
//
