MHAA_STRSJ
ID MHAA_STRSJ Reviewed; 596 AA.
AC C0LTL9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 1.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=3-hydroxy-4-methylanthranilate adenylyltransferase {ECO:0000305};
DE EC=2.7.7.97 {ECO:0000269|PubMed:21612226};
DE AltName: Full=4-MHA-activating enzyme {ECO:0000305};
GN Name=sibE {ECO:0000303|PubMed:19270142};
OS Streptosporangium sibiricum.
OC Bacteria; Actinobacteria; Streptosporangiales; Streptosporangiaceae;
OC Streptosporangium.
OX NCBI_TaxID=457432;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=ATCC 29053 / DSM 44093;
RX PubMed=19270142; DOI=10.1128/aem.02326-08;
RA Li W., Khullar A., Chou S., Sacramo A., Gerratana B.;
RT "Biosynthesis of sibiromycin, a potent antitumor antibiotic.";
RL Appl. Environ. Microbiol. 75:2869-2878(2009).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DOMAIN.
RC STRAIN=ATCC 29053 / DSM 44093;
RX PubMed=21612226; DOI=10.1021/bi2006114;
RA Giessen T.W., Kraas F.I., Marahiel M.A.;
RT "A four-enzyme pathway for 3,5-dihydroxy-4-methylanthranilic acid formation
RT and incorporation into the antitumor antibiotic sibiromycin.";
RL Biochemistry 50:5680-5692(2011).
CC -!- FUNCTION: Involved in the biosynthesis of the antitumor antibiotic
CC sibiromycin (PubMed:19270142, PubMed:21612226). Activates 4-methyl-3-
CC hydroxyanthranilic acid (4-MHA or 3H4MAA), a precursor of the antitumor
CC antibiotic sibiromycin, as adenylate (PubMed:21612226). The activated
CC substrate is then covalently tethered to the thiolation domain
CC (PubMed:21612226). 4-MHA is the preferred substrate, but it can also
CC use 3-hydroxyanthranilic acid (3HAA) and anthranilic acid (AA). Has
CC lower activity with 5-hydroxyanthranilic acid (5HAA) and 3,5-dihydroxy-
CC 4-methylanthranilic acid (3,5DH4MAA) (PubMed:21612226).
CC {ECO:0000269|PubMed:19270142, ECO:0000269|PubMed:21612226}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxy-4-methylanthranilate + ATP + H(+) = 3-hydroxy-4-
CC methylanthranilyl-5'-AMP + diphosphate; Xref=Rhea:RHEA:24980,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:36558, ChEBI:CHEBI:91232; EC=2.7.7.97;
CC Evidence={ECO:0000269|PubMed:21612226};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:19270142,
CC ECO:0000269|PubMed:21612226}.
CC -!- DOMAIN: Contains a A-domain and a T-domain. The A-domain is responsible
CC for selection and activation of a substrate, which is then covalently
CC tethered to the T-domain. {ECO:0000269|PubMed:21612226}.
CC -!- PTM: 4'-phosphopantetheine is transferred from CoA to a specific serine
CC of the apo-form of this carrier protein. {ECO:0000305|PubMed:21612226}.
CC -!- DISRUPTION PHENOTYPE: Inactivation of the gene abolishes sibiromycin
CC production. {ECO:0000269|PubMed:19270142}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; FJ768674; ACN39728.1; -; Genomic_DNA.
DR SMR; C0LTL9; -.
DR KEGG; ag:ACN39728; -.
DR BioCyc; MetaCyc:MON-19743; -.
DR GO; GO:0070566; F:adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IDA:UniProtKB.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; ATP-binding; Nucleotide-binding;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..596
FT /note="3-hydroxy-4-methylanthranilate adenylyltransferase"
FT /id="PRO_0000453571"
FT DOMAIN 512..588
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 548
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 596 AA; 63493 MW; 31FC619E4768C736 CRC64;
MSALPSLRVP TLPVAFEAAA RAAGDRIALE YGSSSITYRE LDAAANRFAR RLLREGVTPG
SRVGLHMTRC LELYIAMIGL LKAGAVVVPL NPSHPVTVRR SVVREADLPL TLRDVPAGLS
SVTVERDVHE LLAAGADLDD TSPGLCTDPE STAFILFTSG STGRPRGVRI AHRGIARVAS
YNGEVEVRPD DCFLQLAPYS FAASTTDIWL SLLHGARVVV LPSQLPSLPK LAHTIKEYGV
TFLNLPGGLM NLLIDAHPEA FAKVRTVIVS GDFPSAPHLA RVMKAVPGTV YNAFGCTENS
ALTAVHPMTP EDLQLGVVPI GLPLPGVGLH VLGEDMTPCA PGEVGEMHIS GAGLAQGYLG
LPEETAAKFP TVDGVRMLRT GDWARTTPAG EVVLVGRTDQ MVKIRGFRVE LREVELAADQ
SGLVEKAVVR AVDATDGQKE LVLFCTTATG EAPSIEALLA DLKSRLPDYM LPARVHHLAE
LPVNVNGKLD RMALREPRAV LVEPDGTAQQ QPVVRDIIAT TVTRLLAVVT GREPIGVSDS
FLASGANSLQ VIQLAASLHD VMGVDVRPED IFQLDNAESL AGHIRALRQG HREVPA
