GRSB_BREBE
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 03-AUG-2022, entry version 68.
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; Firmicutes; 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 PRIDE; P0C064; -.
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:1901566; P:organonitrogen compound biosynthetic process; IEA:UniProt.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 4.
DR Gene3D; 3.30.300.30; -; 4.
DR Gene3D; 3.30.559.10; -; 4.
DR Gene3D; 3.40.50.1820; -; 1.
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.
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 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; SSF47336; SSF47336; 4.
DR SUPFAM; SSF53474; SSF53474; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 4.
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
