ID   GRSB_BREBE              Reviewed;        4450 AA.
AC   P0C064; P14688; Q44928;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   13-SEP-2023, entry version 74.
DE   RecName: Full=Gramicidin S synthase 2;
DE   AltName: Full=Gramicidin S synthase II;
DE   Includes:
DE     RecName: Full=ATP-dependent proline adenylase;
DE              Short=ProA;
DE     AltName: Full=Proline activase;
DE   Includes:
DE     RecName: Full=ATP-dependent valine adenylase;
DE              Short=ValA;
DE     AltName: Full=Valine activase;
DE   Includes:
DE     RecName: Full=ATP-dependent ornithine adenylase;
DE              Short=OrnA;
DE     AltName: Full=Ornithine activase;
DE   Includes:
DE     RecName: Full=ATP-dependent leucine adenylase;
DE              Short=LeuA;
DE     AltName: Full=Leucine activase;
GN   Name=grsB; Synonyms=grs2;
OS   Brevibacillus brevis (Bacillus brevis).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Paenibacillaceae; Brevibacillus.
OX   NCBI_TaxID=1393;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Nagano;
RX   PubMed=7822255; DOI=10.1093/oxfordjournals.jbchem.a124532;
RA   Saito F., Hori K., Kanda M., Kurotsu T., Saito Y.;
RT   "Entire nucleotide sequence for Bacillus brevis Nagano grs2 gene encoding
RT   gramicidin S synthetase 2; a multifunctional peptide synthetas.";
RL   J. Biochem. 116:357-367(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-949.
RC   STRAIN=Nagano;
RX   PubMed=1939016; DOI=10.1093/oxfordjournals.jbchem.a123528;
RA   Hori K., Yamamoto Y., Tokita K., Saito F., Kurotsu T., Kanda M.,
RA   Okamura K., Furuyama J., Saito Y.;
RT   "The nucleotide sequence for a proline-activating domain of gramicidin S
RT   synthetase 2 gene from Bacillus brevis.";
RL   J. Biochem. 110:111-119(1991).
RN   [3]
RP   PROTEIN SEQUENCE OF 2-16, AND CHARACTERIZATION.
RC   STRAIN=Nagano;
RX   PubMed=1917901; DOI=10.1093/oxfordjournals.jbchem.a123454;
RA   Kurotsu T., Hori K., Kanda M., Saito Y.;
RT   "Characterization and location of the L-proline activating fragment from
RT   the multifunctional gramicidin S synthetase 2.";
RL   J. Biochem. 109:763-769(1991).
CC   -!- FUNCTION: This protein is a multifunctional enzyme, able to activate
CC       and polymerize the amino acids Pro, Val, Orn and Leu. Activation sites
CC       for these AA consist of individual domains.
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC       Note=Binds 4 phosphopantetheines covalently.;
CC   -!- PATHWAY: Antibiotic biosynthesis; gramicidin S biosynthesis.
CC   -!- SUBUNIT: Large multienzyme complex of GrsA and GrsB.
CC   -!- DOMAIN: Consists of four modules, and harbors a putative thioesterase
CC       domain at its C-terminal end. Each module incorporates one amino acid
CC       into the peptide product and can be further subdivided into domains
CC       responsible for substrate adenylation, thiolation, condensation (not
CC       for the initiation module), and epimerization (optional), and N
CC       methylation (optional).
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; D29676; BAA06146.1; -; Genomic_DNA.
DR   EMBL; D00938; BAA00778.1; -; Genomic_DNA.
DR   PIR; JX0340; JX0340.
DR   PIR; S20542; YGBSG2.
DR   SMR; P0C064; -.
DR   ESTHER; bacbr-grsb; Thioesterase.
DR   UniPathway; UPA00102; -.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0043604; P:amide biosynthetic process; IEA:UniProt.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0019752; P:carboxylic acid metabolic process; IEA:UniProt.
DR   GO; GO:1901566; P:organonitrogen compound biosynthetic process; IEA:UniProt.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   CDD; cd05930; A_NRPS; 1.
DR   CDD; cd17650; A_NRPS_PpsD_like; 1.
DR   CDD; cd17656; A_NRPS_ProA; 1.
DR   CDD; cd12117; A_NRPS_Srf_like; 1.
DR   CDD; cd19543; DCL_NRPS; 1.
DR   CDD; cd19531; LCL_NRPS-like; 3.
DR   Gene3D; 3.30.300.30; -; 4.
DR   Gene3D; 3.40.50.980; -; 8.
DR   Gene3D; 1.10.1200.10; ACP-like; 4.
DR   Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR   Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 4.
DR   Gene3D; 1.10.287.490; Helix hairpin bin; 1.
DR   Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation domain; 4.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR029058; AB_hydrolase.
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_com.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR001242; Condensatn.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   InterPro; IPR001031; Thioesterase.
DR   NCBIfam; TIGR01733; AA-adenyl-dom; 4.
DR   PANTHER; PTHR45527:SF1; FATTY ACID SYNTHASE; 1.
DR   PANTHER; PTHR45527; NONRIBOSOMAL PEPTIDE SYNTHETASE; 1.
DR   Pfam; PF00501; AMP-binding; 4.
DR   Pfam; PF13193; AMP-binding_C; 4.
DR   Pfam; PF00668; Condensation; 4.
DR   Pfam; PF00550; PP-binding; 4.
DR   Pfam; PF00975; Thioesterase; 1.
DR   SMART; SM00823; PKS_PP; 4.
DR   SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 4.
DR   SUPFAM; SSF47336; ACP-like; 4.
DR   SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR   SUPFAM; SSF52777; CoA-dependent acyltransferases; 8.
DR   PROSITE; PS00455; AMP_BINDING; 4.
DR   PROSITE; PS50075; CARRIER; 4.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 4.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Direct protein sequencing; Hydrolase; Ligase;
KW   Multifunctional enzyme; Phosphopantetheine; Phosphoprotein; Repeat.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:1917901"
FT   CHAIN           2..4450
FT                   /note="Gramicidin S synthase 2"
FT                   /id="PRO_0000193088"
FT   DOMAIN          971..1046
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          2006..2081
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          3051..3126
FT                   /note="Carrier 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          4089..4164
FT                   /note="Carrier 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          467..1044
FT                   /note="Domain 1 (proline-activating)"
FT                   /evidence="ECO:0000250"
FT   REGION          1521..2080
FT                   /note="Domain 2 (valine-activating)"
FT                   /evidence="ECO:0000250"
FT   REGION          2538..3134
FT                   /note="Domain 3 (ornithine-activating)"
FT                   /evidence="ECO:0000250"
FT   REGION          3590..4172
FT                   /note="Domain 4 (leucine-activating)"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1006
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         2041
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         3086
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         4124
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   4450 AA;  508684 MW;  F3197E77BF69316D CRC64;
     MSTFKKEHVQ DMYRLSPMQE GMLFHALLDK DKNAHLVQMS IAIEGIVDVE LLSESLNILI
     DRYDVFRTTF LHEKIKQPLQ VVLKERPVQL QFKDISSLDE EKREQAIEQY KYQDGETVFD
     LTRDPLMRVA IFQTGKVNYQ MIWSFHHILM DGWCFNIIFN DLFNIYLSLK EKKPLQLEAV
     QPYKQFIKWL EKQDKQEALR YWKEHLMNYD QSVTLPKKKA AINNTTYEPA QFRFAFDKVL
     TQQLLRIANQ SQVTLNIVFQ TIWGIVLQKY NSTNDVVYGS VVSGRPSEIS GIEKMVGLFI
     NTLPLRIQTQ KDQSFIELVK TVHQNVLFSQ QHEYFPLYEI QNHTELKQNL IDHIMVIENY
     PLVEELQKNS IMQKVGFTVR DVKMFEPTNY DMTVMVLPRD EISVRLDYNA AVYDIDFIRK
     IEGHMKEVAL CVANNPHVLV QDVPLLTKQE KQHLLVELHD SITEYPDKTI HQLFTEQVEK
     TPEHVAVVFE DEKVTYRELH ERSNQLARFL REKGVKKESI IGIMMERSVE MIVGILGILK
     AGGAFVPIDP EYPKERIGYM LDSVRLVLTQ RHLKDKFAFT KETIVIEDPS ISHELTEEID
     YINESEDLFY IIYTSGTTGK PKGVMLEHKN IVNLLHFTFE KTNINFSDKV LQYTTCSFDV
     CYQEIFSTLL SGGQLYLIRK ETQRDVEQLF DLVKRENIEV LSFPVAFLKF IFNEREFINR
     FPTCVKHIIT AGEQLVVNNE FKRYLHEHNV HLHNHYGPSE THVVTTYTIN PEAEIPELPP
     IGKPISNTWI YILDQEQQLQ PQGIVGELYI SGANVGRGYL NNQELTAEKF FADPFRPNER
     MYRTGDLARW LPDGNIEFLG RADHQVKIRG HRIELGEIEA QLLNCKGVKE AVVIDKADDK
     GGKYLCAYVV MEVEVNDSEL REYLGKALPD YMIPSFFVPL DQLPLTPNGK IDRKSLPNLE
     GIVNTNAKYV VPTNELEEKL AKIWEEVLGI SQIGIQDNFF SLGGHSLKAI TLISRMNKEC
     NVDIPLRLLF EAPTIQEISN YINGAKKESY VAIQPVPEQE YYPVSSVQKR MFILNEFDRS
     GTAYNLPGVM FLDGKLNYRQ LEAAVKKLVE RHEALRTSFH SINGEPVQRV HQNVELQIAY
     SESTEDQVER IIAEFMQPFA LEVAPLLRVG LVKLEAERHL FIMDMHHIIS DGVSMQIMIQ
     EIADLYKEKE LPTLGIQYKD FTVWHNRLLQ SDVIEKQEAY WLNVFTEEIP VLNLPTDYPR
     PTIQSFDGKR FTFSTGKQLM DDLYKVATET GTTLYMVLLA AYNVFLSKYS GQDDIVVGTP
     IAGRSHADVE NMLGMFVNTL AIRSRLNNED TFKDFLANVK QTALHAYENP DYPFDTLVEK
     LGIQRDLSRN PLFDTMFVLQ NTDRKSFEVE QITITPYVPN SRHSKFDLTL EVSEEQNEIL
     LCLEYCTKLF TDKTVERMAG HFLQILHAIV GNPTIIISEI EILSEEEKQH ILFEFNDTKT
     TYPHMQTIQG LFEEQVEKTP DHVAVGWKDQ ALTYRELNER ANQVARVLRQ KGVQPDNIVG
     LLVERSPEML VGIMGILKAG GAYLPLDPEY PADRISYMIQ DCGVRIMLTQ QHLLSLVHDE
     FDCVILDEDS LYKGDSSNLA PVNQAGDLAY IMYTSGSTGK PKGVMVEHRN VIRLVKNTNY
     VQVREDDRII QTGAIGFDAL TFEVFGSLLH GAELYPVTKD VLLDAEKLHK FLQANQITIM
     WLTSPLFNQL SQGTEEMFAG LRSLIVGGDA LSPKHINNVK RKCPNLTMWN GYGPTENTTF
     STCFLIDKEY DDNIPIGKAI SNSTVYIMDR YGQLQPVGVP GELCVGGDGV ARGYMNQPAL
     TEEKFVPNPF APGERMYRTG DLARWLPDGT IEYLGRIDQQ VKIRGYRIEP GEIETLLVKH
     KKVKESVIMV VEDNNGQKAL CAYYVPEEEV TVSELREYIA KELPVYMVPA YFVQIEQMPL
     TQNGKVNRSA LPKPDGEFGT ATEYVAPSSD IEMKLAEIWH NVLGVNKIGV LDNFFELGGH
     SLRAMTMISQ VHKEFDVELP LKVLFETPTI SALAQYIADG EKGMYLAIQP VTPQDYYPVS
     SAQKRMYILY EFEGAGITYN VPNVMFIEGK LDYQRFEYAI KSLINRHEAL RTSFYSLNGE
     PVQRVHQNVE LQIAYSEAKE DEIEQIVESF VQPFDLEIAP ALRVGLVKLA SDRHLFLMDM
     HHIISDGVSM QIITKEIADL YKGKELAELH IQYKDFAVWQ NEWFQSAALE KQKTYWLNTF
     AEDIPVLNLS TDYPRPTIQS FEGDIVTFSA GKQLAEELKR LATETGTTLY MLLLAAYNVL
     LHKYSGQEEI VVGTPIAGRS HADVENIVGM FVNTLALKNT PIAVRTFHEF LLEVKQNALE
     AFENQDYPFE NLIEKLQVRR DLSRNPLFDT MFSLSNIDEQ VEIGIEGLSF SPYEMQYWIA
     KFDISFDILE KQDDIQFYFN YCTNLFKKET IERLATHFMH ILQEIVINPE IKLCEINMLS
     EEEQQRVLYD FNGTDATYAT NKIFHELFEE QVEKTPDHIA VIDEREKLSY QELNAKANQL
     ARVLRQKGVQ PNSMVGIMVD RSLDMIVGML GVLKAGGAYV PIDIDYPQER ISYMMEDSGA
     ALLLTQQKLT QQIAFSGDIL YLDQEEWLHE EASNLEPIAR PQDIAYIIYT SGTTGKPKGV
     MIEHQSYVNV AMAWKDAYRL DTFPVRLLQM ASFAFDVSAG DFARALLTGG QLIVCPNEVK
     MDPASLYAII KKYDITIFEA TPALVIPLME YIYEQKLDIS QLQILIVGSD SCSMEDFKTL
     VSRFGSTIRI VNSYGVTEAC IDSSYYEQPL SSLHVTGTVP IGKPYANMKM YIMNQYLQIQ
     PVGVIGELCI GGAGVARGYL NRPDLTAEKF VPNPFVPGEK LYRTGDLARW MPDGNVEFLG
     RNDHQVKIRG IRIELGEIEA QLRKHDSIKE ATVIAREDHM KEKYLCAYMV TEGEVNVAEL
     RAYLATDLPA AMIPSYFVSL EAMPLTANGK IDKRSLPEPD GSISIGTEYV APRTMLEGKL
     EEIWKDVLGL QRVGIHDDFF TIGGHSLKAM AVISQVHKEC QTEVPLRVLF ETPTIQGLAK
     YIEETDTEQY MAIQPVSGQD YYPVSSAQKR MFIVNQFDGV GISYNMPSIM LIEGKLERTR
     LESAFKRLIE RHESLRTSFE IINGKPVQKI HEEADFNMSY QVASNEQVEK MIDEFIQPFD
     LSVAPLLRVE LLKLEEDRHV LIFDMHHIIS DGISSNILMK ELGELYQGNA LPELRIQYKD
     FAVWQNEWFQ SEAFKKQEEY WVNVFADERP ILDIPTDYPR PMQQSFDGAQ LTFGTGKQLM
     DGLYRVATET GTTLYMVLLA AYNVLLSKYS GQEDIIVGTP IVGRSHTDLE NIVGMFVNTL
     AMRNKPEGEK TFKAFVSEIK QNALAAFENQ DYPFEELIEK LEIQRDLSRN PLFDTLFSLQ
     NIGEESFELA ELTCKPFDLV SKLEHAKFDL SLVAVEKEEE IAFGLQYCTK LYKEKTVEQL
     AQHFIQIVKA IVENPDVKLS DIDMLSEEEK KQIMLEFNDT KIQYPQNQTI QELFEEQVKK
     TPEHIAIVWE GQALTYHELN IKANQLARVL REKGVTPNHP VAIMTERSLE MIVGIFSILK
     AGGAYVPIDP AYPQERIQYL LEDSGATLLL TQSHVLNKLP VDIEWLDLTD EQNYVEDGTN
     LPFMNQSTDL AYIIYTSGTT GKPKGVMIEH QSIINCLQWR KEEYEFGPGD TALQVFSFAF
     DGFVASLFAP ILAGATSVLP KEEEAKDPVA LKKLIASEEI THYYGVPSLF SAILDVSSSK
     DLQNLRCVTL GGEKLPAQIV KKIKEKNKEI EVNNEYGPTE NSVVTTIMRD IQVEQEITIG
     CPLSNVDVYI VNCNHQLQPV GVVGELCIGG QGLARGYLNK PELTADKFVV NPFVPGERMY
     KTGDLAKWRS DGMIEYVGRV DEQVKVRGYR IELGEIESAI LEYEKIKEAV VIVSEHTASE
     QMLCAYIVGE EDVLTLDLRS YLAKLLPSYM IPNYFIQLDS IPLTPNGKVD RKALPEPQTI
     GLMAREYVAP RNEIEAQLVL IWQEVLGIEL IGITDNFFEL GGHSLKATLL VAKIYEYMQI
     EMPLNVVFKH STIMKIAEYI THQESENNVH QPILVNVEAD REALSLNGEK QRKNIELPIL
     LNEETDRNVF LFAPIGAQGV FYKKLAEQIP TASLYGFDFI EDDDRIQQYI ESMIQTQSDG
     QYVLIGYSSG GNLAFEVAKE MERQGYSVSD LVLFDVYWKG KVFEQTKEEE EENIKIIMEE
     LRENPGMFNM TREDFELYFA NEFVKQSFTR KMRKYMSFYT QLVNYGEVEA TIHLIQAEFE
     EEKIDENEKA DEEEKTYLEE KWNEKAWNKA AKRFVKYNGY GAHSNMLGGD GLERNSSILK
     QILQGTFVVK
//