ASPG_DICCH
ID ASPG_DICCH Reviewed; 348 AA.
AC P06608;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=L-asparaginase;
DE Short=L-ASNase;
DE EC=3.5.1.1;
DE AltName: Full=L-asparagine amidohydrolase;
DE Flags: Precursor;
GN Name=ansB; Synonyms=asn;
OS Dickeya chrysanthemi (Pectobacterium chrysanthemi) (Erwinia chrysanthemi).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Pectobacteriaceae; Dickeya.
OX NCBI_TaxID=556;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NCPPB 1066;
RX PubMed=3026924; DOI=10.1016/0378-1119(86)90163-0;
RA Minton N.P., Bullman H.M.S., Scawen M.D., Atkinson T., Gilbert H.J.;
RT "Nucleotide sequence of the Erwinia chrysanthemi NCPPB 1066 L-asparaginase
RT gene.";
RL Gene 46:25-35(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NCPPB 1125;
RX PubMed=3194219; DOI=10.1093/nar/16.21.10385;
RA Filpula D., Nagle J.W., Pulford S., Anderson D.M.;
RT "Sequence of L-asparaginase gene from Erwinia chrysanthemi NCPPB 1125.";
RL Nucleic Acids Res. 16:10385-10385(1988).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=3379033; DOI=10.1016/s0021-9258(18)68344-9;
RA Tanaka S., Robinson E.A., Appella E., Miller M., Ammon H.L., Roberts J.,
RA Weber I.T., Wlodawer A.;
RT "Structures of amidohydrolases. Amino acid sequence of a glutaminase-
RT asparaginase from Acinetobacter glutaminasificans and preliminary
RT crystallographic data for an asparaginase from Erwinia chrysanthemi.";
RL J. Biol. Chem. 263:8583-8591(1988).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH ASPARTIC ACID, ACTIVE
RP SITE, AND SUBUNIT.
RX PubMed=8348975; DOI=10.1016/0014-5793(93)80943-o;
RA Miller M.M., Rao J.K.M., Wlodawer A., Gribskov M.R.;
RT "A left-handed crossover involved in amidohydrolase catalysis. Crystal
RT structure of Erwinia chrysanthemi L-asparaginase with bound L-aspartate.";
RL FEBS Lett. 328:275-279(1993).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 22-348 IN COMPLEXES WITH GLUTAMIC
RP ACID; ASPARTIC ACID AND SUCCINIC ACID.
RX PubMed=11341830; DOI=10.1021/bi0029595;
RA Aghaiypour K., Wlodawer A., Lubkowski J.;
RT "Structural basis for the activity and substrate specificity of Erwinia
RT chrysanthemi L-asparaginase.";
RL Biochemistry 40:5655-5664(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 22-348 IN COMPLEX WITH INHIBITOR
RP 6-DIAZO-5-OXY-NORLEUCINE, AND ACTIVE SITE.
RX PubMed=11755201; DOI=10.1016/s0167-4838(01)00270-9;
RA Aghaiypour K., Wlodawer A., Lubkowski J.;
RT "Do bacterial L-asparaginases utilize a catalytic triad Thr-Tyr-Glu?";
RL Biochim. Biophys. Acta 1550:117-128(2001).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 22-348, AND SUBUNIT.
RX PubMed=12499544; DOI=10.1107/s0907444902019443;
RA Lubkowski J., Dauter M., Aghaiypour K., Wlodawer A., Dauter Z.;
RT "Atomic resolution structure of Erwinia chrysanthemi L-asparaginase.";
RL Acta Crystallogr. D 59:84-92(2003).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-asparagine = L-aspartate + NH4(+);
CC Xref=Rhea:RHEA:21016, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:58048; EC=3.5.1.1;
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11755201,
CC ECO:0000269|PubMed:12499544, ECO:0000269|PubMed:8348975}.
CC -!- PHARMACEUTICAL: Available under the name Erwinase (Beaufour Ipsen).
CC Used as an antineoplastic in chemotherapy. Reduces the quantity of
CC asparagine available to cancer cells.
CC -!- MISCELLANEOUS: The sequence of strain NCPPB 1066 is shown.
CC -!- SIMILARITY: Belongs to the asparaginase 1 family. {ECO:0000305}.
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DR EMBL; X14777; CAA32884.1; -; Genomic_DNA.
DR EMBL; X12746; CAA31239.1; -; Genomic_DNA.
DR PIR; A26054; A26054.
DR PDB; 1HFJ; X-ray; 2.40 A; A/C=22-348.
DR PDB; 1HFK; X-ray; 2.17 A; A/C=22-348.
DR PDB; 1HFW; X-ray; 1.80 A; A/B/C/D=22-348.
DR PDB; 1HG0; X-ray; 1.90 A; A/B/C/D=22-348.
DR PDB; 1HG1; X-ray; 1.80 A; A/B/C/D=22-348.
DR PDB; 1JSL; X-ray; 1.70 A; A/B/C/D=22-348.
DR PDB; 1JSR; X-ray; 1.70 A; A/B/C/D=22-348.
DR PDB; 1O7J; X-ray; 1.00 A; A/B/C/D=22-348.
DR PDB; 5F52; X-ray; 1.63 A; A/B/C/D=23-348.
DR PDB; 5HW0; X-ray; 1.70 A; A/B/C/D=23-348.
DR PDB; 5I3Z; X-ray; 2.05 A; A/B/C/D=23-348.
DR PDB; 5I48; X-ray; 1.50 A; A/B/C/D=23-348.
DR PDB; 5I4B; X-ray; 1.60 A; A/B/C=23-348.
DR PDB; 6PAE; X-ray; 1.60 A; A/B/C/D=22-348.
DR PDBsum; 1HFJ; -.
DR PDBsum; 1HFK; -.
DR PDBsum; 1HFW; -.
DR PDBsum; 1HG0; -.
DR PDBsum; 1HG1; -.
DR PDBsum; 1JSL; -.
DR PDBsum; 1JSR; -.
DR PDBsum; 1O7J; -.
DR PDBsum; 5F52; -.
DR PDBsum; 5HW0; -.
DR PDBsum; 5I3Z; -.
DR PDBsum; 5I48; -.
DR PDBsum; 5I4B; -.
DR PDBsum; 6PAE; -.
DR AlphaFoldDB; P06608; -.
DR SMR; P06608; -.
DR ChEMBL; CHEMBL1075190; -.
DR DrugBank; DB02233; 6-hydroxy-D-norleucine.
DR DrugBank; DB03412; 6-hydroxynorleucine.
DR DrugBank; DB02655; D-Aspartic Acid.
DR Allergome; 8366; Erw ch Asparaginase.
DR PRIDE; P06608; -.
DR BRENDA; 3.5.1.1; 2141.
DR EvolutionaryTrace; P06608; -.
DR GO; GO:0110165; C:cellular anatomical entity; IEA:UniProt.
DR GO; GO:0004067; F:asparaginase activity; IEA:UniProtKB-EC.
DR GO; GO:0006528; P:asparagine metabolic process; IEA:InterPro.
DR Gene3D; 3.40.50.1170; -; 1.
DR Gene3D; 3.40.50.40; -; 1.
DR InterPro; IPR004550; AsnASE_II.
DR InterPro; IPR036152; Asp/glu_Ase-like_sf.
DR InterPro; IPR006034; Asparaginase/glutaminase-like.
DR InterPro; IPR020827; Asparaginase/glutaminase_AS1.
DR InterPro; IPR027475; Asparaginase/glutaminase_AS2.
DR InterPro; IPR040919; Asparaginase_C.
DR InterPro; IPR027473; L-asparaginase_C.
DR InterPro; IPR027474; L-asparaginase_N.
DR InterPro; IPR037152; L-asparaginase_N_sf.
DR Pfam; PF00710; Asparaginase; 1.
DR Pfam; PF17763; Asparaginase_C; 1.
DR PIRSF; PIRSF001220; L-ASNase_gatD; 1.
DR PRINTS; PR00139; ASNGLNASE.
DR SMART; SM00870; Asparaginase; 1.
DR SUPFAM; SSF53774; SSF53774; 1.
DR TIGRFAMs; TIGR00520; asnASE_II; 1.
DR PROSITE; PS00144; ASN_GLN_ASE_1; 1.
DR PROSITE; PS00917; ASN_GLN_ASE_2; 1.
DR PROSITE; PS51732; ASN_GLN_ASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Pharmaceutical; Signal.
FT SIGNAL 1..21
FT CHAIN 22..348
FT /note="L-asparaginase"
FT /id="PRO_0000002358"
FT DOMAIN 26..348
FT /note="Asparaginase/glutaminase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01068"
FT ACT_SITE 36
FT /note="O-isoaspartyl threonine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10099,
FT ECO:0000255|PROSITE-ProRule:PRU10100,
FT ECO:0000269|PubMed:11755201, ECO:0000269|PubMed:8348975"
FT BINDING 83
FT /ligand="substrate"
FT BINDING 116..117
FT /ligand="substrate"
FT VARIANT 177
FT /note="L -> I (in strain: NCPPB 1125)"
FT VARIANT 199
FT /note="K -> R (in strain: NCPPB 1125)"
FT VARIANT 288
FT /note="M -> L (in strain: NCPPB 1125)"
FT VARIANT 295
FT /note="I -> M (in strain: NCPPB 1125)"
FT STRAND 27..35
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:5HW0"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:5F52"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:5I48"
FT HELIX 57..63
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 65..69
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 72..81
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 88..102
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:1O7J"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:5I48"
FT HELIX 119..129
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 152..164
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:1O7J"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:1O7J"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 253..260
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 264..271
FT /evidence="ECO:0007829|PDB:1O7J"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 278..289
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 293..303
FT /evidence="ECO:0007829|PDB:1O7J"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 321..331
FT /evidence="ECO:0007829|PDB:1O7J"
FT TURN 332..334
FT /evidence="ECO:0007829|PDB:1O7J"
FT HELIX 338..347
FT /evidence="ECO:0007829|PDB:1O7J"
SQ SEQUENCE 348 AA; 37575 MW; C6A4C188E569D9A6 CRC64;
MERWFKSLFV LVLFFVFTAS AADKLPNIVI LATGGTIAGS AATGTQTTGY KAGALGVDTL
INAVPEVKKL ANVKGEQFSN MASENMTGDV VLKLSQRVNE LLARDDVDGV VITHGTDTVE
ESAYFLHLTV KSDKPVVFVA AMRPATAISA DGPMNLLEAV RVAGDKQSRG RGVMVVLNDR
IGSARYITKT NASTLDTFKA NEEGYLGVII GNRIYYQNRI DKLHTTRSVF DVRGLTSLPK
VDILYGYQDD PEYLYDAAIQ HGVKGIVYAG MGAGSVSVRG IAGMRKAMEK GVVVIRSTRT
GNGIVPPDEE LPGLVSDSLN PAHARILLML ALTRTSDPKV IQEYFHTY
