DDAF_ENTAG
ID DDAF_ENTAG Reviewed; 424 AA.
AC E2JA31;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Dapdiamide A synthase {ECO:0000305};
DE EC=6.3.2.47 {ECO:0000269|PubMed:19807062, ECO:0000269|PubMed:20945916};
DE AltName: Full=ATP-dependent N-fumaramoyl-DAP-amino acid ligase {ECO:0000303|PubMed:19807062};
GN Name=ddaF {ECO:0000303|PubMed:19807062};
GN Synonyms=apvF {ECO:0000312|EMBL:AFJ97210.1};
OS Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Erwiniaceae; Pantoea; Pantoea agglomerans group.
OX NCBI_TaxID=549;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=CU0119;
RX PubMed=20945916; DOI=10.1021/ja1072367;
RA Hollenhorst M.A., Bumpus S.B., Matthews M.L., Bollinger J.M. Jr.,
RA Kelleher N.L., Walsh C.T.;
RT "The nonribosomal peptide synthetase enzyme DdaD tethers N(beta)-
RT fumaramoyl-l-2,3-diaminopropionate for Fe(II)/alpha-ketoglutarate-dependent
RT epoxidation by DdaC during dapdiamide antibiotic biosynthesis.";
RL J. Am. Chem. Soc. 132:15773-15781(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=48b/90;
RX PubMed=23233458; DOI=10.1002/mbo3.43;
RA Sammer U.F., Reiher K., Spiteller D., Wensing A., Volksch B.;
RT "Assessment of the relevance of the antibiotic 2-amino-3-(oxirane-2,3-
RT dicarboxamido)-propanoyl-valine from Pantoea agglomerans biological control
RT strains against bacterial plant pathogens.";
RL MicrobiologyOpen 1:438-449(2012).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=CU0119;
RX PubMed=19807062; DOI=10.1021/bi9013165;
RA Hollenhorst M.A., Clardy J., Walsh C.T.;
RT "The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-
RT dipeptide scaffold of the dapdiamide antibiotics.";
RL Biochemistry 48:10467-10472(2009).
CC -!- FUNCTION: Involved in dapdiamide antibiotics biosynthesis
CC (PubMed:19807062, PubMed:20945916). Ligates N-beta-fumaramoyl-DAP and
CC valine, isoleucine or leucine to form dapdiamides A, B or C,
CC respectively (PubMed:19807062). Also ligates N-beta-epoxysuccinamoyl-
CC DAP and valine to form dapdiamide E (PubMed:20945916).
CC {ECO:0000269|PubMed:19807062, ECO:0000269|PubMed:20945916}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-[[[(2R,3R)-3-carboxyoxiran-2-yl]carbonyl]amino]-L-alanine +
CC ATP + L-valine = ADP + dapdiamide E + H(+) + phosphate;
CC Xref=Rhea:RHEA:45080, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57762, ChEBI:CHEBI:84912,
CC ChEBI:CHEBI:84913, ChEBI:CHEBI:456216; EC=6.3.2.47;
CC Evidence={ECO:0000269|PubMed:20945916};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-valine + N(3)-fumaramoyl-(S)-2,3-diaminopropanoate =
CC ADP + dapdiamide A + H(+) + phosphate; Xref=Rhea:RHEA:44344,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57762, ChEBI:CHEBI:84320, ChEBI:CHEBI:84331,
CC ChEBI:CHEBI:456216; EC=6.3.2.47;
CC Evidence={ECO:0000269|PubMed:19807062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-isoleucine + N(3)-fumaramoyl-(S)-2,3-diaminopropanoate
CC = ADP + dapdiamide B + H(+) + phosphate; Xref=Rhea:RHEA:44348,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58045, ChEBI:CHEBI:84321, ChEBI:CHEBI:84331,
CC ChEBI:CHEBI:456216; EC=6.3.2.47;
CC Evidence={ECO:0000269|PubMed:19807062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-leucine + N(3)-fumaramoyl-(S)-2,3-diaminopropanoate =
CC ADP + dapdiamide C + H(+) + phosphate; Xref=Rhea:RHEA:44352,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57427, ChEBI:CHEBI:84322, ChEBI:CHEBI:84331,
CC ChEBI:CHEBI:456216; EC=6.3.2.47;
CC Evidence={ECO:0000269|PubMed:19807062};
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 1 magnesium or manganese ion per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.26 mM for valine {ECO:0000269|PubMed:19807062};
CC KM=0.83 mM for isoleucine {ECO:0000269|PubMed:19807062};
CC KM=7.82 mM for leucine {ECO:0000269|PubMed:19807062};
CC KM=72 uM for N-beta-fumaramoyl-DAP {ECO:0000269|PubMed:20945916};
CC KM=53 uM for N-beta-epoxysuccinamoyl-DAP
CC {ECO:0000269|PubMed:20945916};
CC Note=kcat is 8.1 min(-1) with valine as substrate. kcat is 9.5 min(-
CC 1) with isoleucine as substrate. kcat is 11.2 min(-1) with leucine as
CC substrate (PubMed:19807062). kcat is 21 min(-1) with N-beta-
CC fumaramoyl-DAP as substrate. kcat is 181 min(-1) with N-beta-
CC epoxysuccinamoyl-DAP as substrate (PubMed:20945916).
CC {ECO:0000269|PubMed:19807062, ECO:0000269|PubMed:20945916};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:19807062,
CC ECO:0000269|PubMed:20945916}.
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DR EMBL; HQ130277; ADN39488.1; -; Genomic_DNA.
DR EMBL; JQ901494; AFJ97210.1; -; Genomic_DNA.
DR RefSeq; WP_033781244.1; NZ_JPOT02000004.1.
DR AlphaFoldDB; E2JA31; -.
DR SMR; E2JA31; -.
DR KEGG; ag:ADN39488; -.
DR BioCyc; MetaCyc:MON-19476; -.
DR BRENDA; 6.3.2.47; 2084.
DR BRENDA; 6.3.2.B15; 2084.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR011761; ATP-grasp.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; ATP-binding; Ligase; Magnesium; Manganese;
KW Metal-binding; Nucleotide-binding.
FT CHAIN 1..424
FT /note="Dapdiamide A synthase"
FT /id="PRO_0000434792"
FT DOMAIN 120..318
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 147..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 275
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 287
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
SQ SEQUENCE 424 AA; 46884 MW; F9A9BA70B5825E84 CRC64;
MSILNNKEVI VIIDAWSGGK HLIPAFQALG YFCLHVQSTF LPEVFIADNQ LAIARSDRHI
VHDGNIETLL SQLQPYTIKA ILAGSEGAVG LADCLNDALE LTFSNQFELS AARRNKYLMQ
EQLALKGVAS INQQLAGHSD ELKQWLAGHA HWPVVLKPIQ SAGTDGVFIC HDLAQALQAF
EAILAKKDFF GSPNREVLCQ EFLAGEEFVV NGIACQGEYF FTELWQSKKQ QRNGFPVYET
QYLHYQNDAG FDVLTAYTVQ VCQTLGINNG AFHAEVMMTS GGPVLIEIGA RVAGGADPYI
IEECLGHSQI SKLAQAVLHP AKFLQECRRQ HDFSGHRRAA YVYMISPSPG RVQVSPEEKF
IKIDGVISIN YHYAPGDIQQ ETCDLLSSPG VIIAIRDNPA LLKQTIAEIR DVEADFYHLG
LIDE
