ID TYCC_BREPA Reviewed; 6486 AA.
AC O30409;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 19-JAN-2010, entry version 79.
DE RecName: Full=Tyrocidine synthetase 3;
DE AltName: Full=Tyrocidine synthetase III;
DE Includes:
DE RecName: Full=ATP-dependent asparagine adenylase;
DE Short=AsnA;
DE AltName: Full=Asparagine activase;
DE Includes:
DE RecName: Full=ATP-dependent glutamine adenylase;
DE Short=GlnA;
DE AltName: Full=Glutamine activase;
DE Includes:
DE RecName: Full=ATP-dependent tyrosine adenylase;
DE Short=TyrA;
DE AltName: Full=Tyrosine 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=tycC;
OS Brevibacillus parabrevis.
OC Bacteria; Firmicutes; Bacillales; Paenibacillaceae; Brevibacillus.
OX NCBI_TaxID=54914;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 8185 / IAM 1031 / IFO 3331 / NCDO 717 / NCIB 8598;
RX MEDLINE=98012987; PubMed=9352938;
RA Mootz H.D., Marahiel M.A.;
RT "The tyrocidine biosynthesis operon of Bacillus brevis: complete
RT nucleotide sequence and biochemical characterization of functional
RT internal adenylation domains.";
RL J. Bacteriol. 179:6843-6850(1997).
RN [2]
RP STRUCTURE BY NMR OF 3032-3113.
RX MEDLINE=20264307; PubMed=10801488; DOI=10.1016/S0969-2126(00)00120-9;
RA Weber T., Baumgartner R., Renner C., Marahiel M.A., Holak T.A.;
RT "Solution structure of PCP, a prototype for the peptidyl carrier
RT domains of modular peptide synthetases.";
RL Structure 8:407-418(2000).
CC -!- FUNCTION: Incorporates six amino acids (for tyrocidine A, Asn,
CC Gln, Tyr, Val, Orn, and Leu) in their L-configuration into the
CC peptide product.
CC -!- COFACTOR: Binds 6 phosphopantetheines covalently (By similarity).
CC -!- PATHWAY: Antibiotic biosynthesis; tyrocidine biosynthesis.
CC -!- SUBUNIT: Large multienzyme complex of tycA, tycB and tycC.
CC -!- DOMAIN: Consists of six modules, and harbors a putative
CC thioesterase domain at its C-terminal end. Each module
CC incorporates one amino acid into the peptide product and can be
CC further subdivided into domains responsible for substrate
CC adenylation, thiolation, condensation (not for the initiation
CC module), and epimerization (optional), and N methylation
CC (optional).
CC -!- MISCELLANEOUS: Tyrocidine is a mixture of four cyclic
CC decapeptides, tyrocidine A (D-Phe-Pro-Phe-D-Phe-Asn-Gln-Tyr-Val-
CC Orn-Leu), B, C, and D, in which Phe, at positions 3, 4, and Tyr
CC residues are gradually replaced by Trp, depending on the relative
CC concentrations of these amino acids in the growth medium.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme
CC family.
CC -!- SIMILARITY: Contains 6 acyl carrier domains.
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DR EMBL; AF004835; AAC45930.1; -; Genomic_DNA.
DR PDB; 1DNY; NMR; -; A=3032-3113.
DR PDB; 2GDW; NMR; -; A=3033-3113.
DR PDB; 2GDX; NMR; -; A=3033-3113.
DR PDB; 2GDY; NMR; -; A=3033-3113.
DR PDB; 2GE1; Model; -; B=3033-3113.
DR PDB; 2JGP; X-ray; 1.85 A; A=5116-5633.
DR PDB; 2K2Q; NMR; -; A=3033-3112.
DR PDBsum; 1DNY; -.
DR PDBsum; 2GDW; -.
DR PDBsum; 2GDX; -.
DR PDBsum; 2GDY; -.
DR PDBsum; 2GE1; -.
DR PDBsum; 2JGP; -.
DR PDBsum; 2K2Q; -.
DR DIP; DIP-29492N; -.
DR GO; GO:0000036; F:acyl carrier activity; IEA:InterPro.
DR GO; GO:0048037; F:cofactor binding; IEA:InterPro.
DR GO; GO:0016788; F:hydrolase activity, acting on ester bonds; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR009081; Acyl_carrier_prot-like.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR006163; Phsphopanteth_bd.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR006162; PPantetheine_attach_site.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 6.
DR Pfam; PF00668; Condensation; 6.
DR Pfam; PF00550; PP-binding; 6.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 6.
DR PROSITE; PS50075; ACP_DOMAIN; 6.
DR PROSITE; PS00455; AMP_BINDING; 6.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Ligase; Multifunctional enzyme;
KW Phosphopantetheine; Repeat.
FT CHAIN 1 6486 Tyrocidine synthetase 3.
FT /FTId=PRO_0000193095.
FT DOMAIN 970 1037 Acyl carrier 1.
FT DOMAIN 2007 2074 Acyl carrier 2.
FT DOMAIN 3045 3112 Acyl carrier 3.
FT DOMAIN 4080 4147 Acyl carrier 4.
FT DOMAIN 5124 5191 Acyl carrier 5.
FT DOMAIN 6167 6234 Acyl carrier 6.
FT REGION 466 1038 Domain 1 (asparagine-activating).
FT REGION 1521 2070 Domain 2 (glutamine-activating).
FT REGION 2536 3113 Domain 3 (tyrosine-activating).
FT REGION 3590 4149 Domain 4 (valine-activating).
FT REGION 4606 5203 Domain 5 (ornithine-activating).
FT REGION 5658 6245 Domain 6 (leucine-activating).
FT MOD_RES 1000 1000 O-(pantetheine 4'-phosphoryl)serine (By
FT similarity).
FT MOD_RES 2037 2037 O-(pantetheine 4'-phosphoryl)serine (By
FT similarity).
FT MOD_RES 3075 3075 O-(pantetheine 4'-phosphoryl)serine.
FT MOD_RES 4110 4110 O-(pantetheine 4'-phosphoryl)serine (By
FT similarity).
FT MOD_RES 5154 5154 O-(pantetheine 4'-phosphoryl)serine (By
FT similarity).
FT MOD_RES 6197 6197 O-(pantetheine 4'-phosphoryl)serine (By
FT similarity).
FT HELIX 3044 3057
FT HELIX 3076 3088
FT HELIX 3095 3100
FT HELIX 3104 3112
FT HELIX 5123 5136
FT TURN 5147 5151
FT HELIX 5154 5168
FT HELIX 5174 5179
FT HELIX 5183 5192
FT STRAND 5208 5211
FT HELIX 5214 5225
FT TURN 5229 5232
FT STRAND 5236 5242
FT HELIX 5246 5259
FT HELIX 5261 5264
FT STRAND 5265 5270
FT STRAND 5273 5278
FT STRAND 5287 5290
FT HELIX 5293 5302
FT STRAND 5315 5323
FT STRAND 5326 5334
FT HELIX 5335 5337
FT HELIX 5340 5354
FT HELIX 5366 5376
FT HELIX 5380 5392
FT STRAND 5415 5422
FT HELIX 5425 5438
FT HELIX 5442 5458
FT STRAND 5463 5469
FT HELIX 5475 5477
FT STRAND 5486 5492
FT HELIX 5500 5516
FT HELIX 5522 5528
FT STRAND 5542 5548
FT STRAND 5558 5564
FT STRAND 5575 5584
FT STRAND 5589 5596
FT TURN 5597 5599
FT HELIX 5602 5621
FT HELIX 5627 5629
SQ SEQUENCE 6486 AA; 724033 MW; 4934900AF07DF786 CRC64;
MKKQENIAKI YPLTPLQEGM LFHAVTDTGS SAYCLQMSAT IEGDFHLPLF EKSLNKLVEN
YEVLRTAFVY QNMQRPRQVV FKERKVTVPC ENIAHLPSAE QDAYIQAYTK QHHAFDLTKD
NLMKAAIFQT AENKYRLVWA FHHIIVDGWT LGVLLHKLLT YYAALRKGEP IPREATKPYS
EYIKWLDKQN KDEALAYWQN YLAGYDHQAA FPKKKLGTEA SRYEHVEAMF TIAPEKTQQL
IQIANQNQAT MSSVFQALWG ILASTYKNAD DVVFGSVVSG RPPQIQGIES MVGLFINTIP
TRVQTNKQQT FSELLQTVQK QALASATYDF APLYEIQSTT VLKQELIDHL VTFENYPDHS
MKHLEESLGF QFTVESGDEQ TSYDLNVVVA LAPSNELYVK LSYNAAVYES SFVNRIEGHL
RTVIDQVIGN PHVHLHEIGI ITEEEKQQLL VAYNDTAAEY PRDKTIFELI AEQASRTPAK
AAVVCGEDTL TYQELMERSA QLANALREKG IASGSIVSIM AEHSLELIVA IMAVLRSGAA
YLPIDPEYPQ DRIQYLLDDS QTTLLLTQSH LQPNIRFAGS VLYLDDRSLY EGGSTSFAPE
SKPDDLAYMI YTSGSTGNPK GAMITHQGLV NYIWWANKVY VQGEAVDFPL YSSISFDLTV
TSIFTPLLSG NTIHVYRGAD KVQVILDIIK DNKVGIIKLT PTHLKLIEHI DGKASSIRRF
IVGGENLPTK LAKQIYDHFG ENVQIFNEYG PTETVVGCMI YLYDPQTTTQ ESVPIGVPAD
NVQLYLLDAS MQPVPVGSLG EMYIAGDGVA KGYFNRPELT KEKFIDNPFR PGTKMYRTGD
LAKWLPDGNM EYAGRMDYQV KIRGHRIEMG EIETRLTQHE AVKEAVVIVE KDESGQNVLY
AYLVSERELT VAELREFLGR TLPSYMIPSF FIRLAEIPLT ANGKVERKKL PKPAGAVVTG
TAYAAPQNEI EAKLAEIWQQ VLGISQVGIH DDFFDLGGHS LKAMTVVFQV SKALEVELPV
KALFEHPTVA ELARFLSRSE KTEYTAIQPV AAQEFYPVSS AQKRMYILQQ FEGNGISYNI
SGAILLEGKL DYARFASAVQ QLAERHEALR TSFHRIDGEP VQKVHEEVEV PLFMLEAPED
QAEKIMREFV RPFDLGVAPL MRTGLLKLGK DRHLFLLDMH HIISDGVSSQ ILLREFAELY
QGADLQPLSL QYKDFAAWQN ELFQTEAYKK QEQHWLNTFA DEIPLLNLPT DYPRPSVQSF
AGDLVLFAAG KELLERLQQV ASETGTTLYM ILLAAYNVLL SKYTGQEDII VGTPVAGRSH
ADVENIMGIF VNTLALRNQP ASSKTFAQFL QEVKQNALAA YDHQDYPFEE LVEKLAIQRD
ISRNPLFDTL FSLENANQQS LAIAELTASP YELFNKISKF DLALNASESP ADIQFQLTFA
TKLFKKETVE RMARHYLEIL RWISEQPTAS LADIDMMTEA EKRTLLLNVN DTFVERTAAT
ALHQLVEEQA ARTPDEVAVV YEEYALTYRE LNARANQLAR LLRSHGTGPD TLIGIMVDRS
PGMVVGMLAV LKAGGAYTPI DPSYPPERIQ YMLSDSQAPI LLTQRHLQEL AAYQGEIIDV
DEEAIYTGAD TNLDNVAGKD DLAYVIYTSG STGNPKGVMI SHQAICNHML WMRETFPLTT
EDAVLQKTPF SFDASVWEFY LPLITGGQLV LAKPDGHRDI AYMTRLIRDE KITTLQMVPS
LLDLVMTDPG WSACTSLQRV FCGGEALTPA LVSRFYETQQ AQLINLYGPT ETTIDATYWP
CPRQQEYSAI PIGKPIDNVR LYVVNASNQL QPVGVAGELC IAGDGLARGY WQREELTKAS
FVDNPFEPGG TMYRTGDMVR YLPDGHIEYL GRIDHQVKIR GHRIELGEIE ATLLQHEAVK
AVVVMARQDG KGQNSLYAYV VAEQDIQTAE LRTYLSATLP AYMVPSAFVF LEQLPLSANG
KVDRKALPQP EDAAASAAVY VAPRNEWEAK LAAIWESVLG VEPIGVHDHF FELGGHSLKA
MHVISLLQRS FQVDVPLKVL FESPTIAGLA PLVAAARKGT YTAIPPVEKQ EYYPVSAAQK
RMFILQQMEG AGISYNMPGF MYLDGKLDTE RLQQALKSLV QRHESLRTSF HSVQGETVQR
VHDDVDLAIS FGEATEAETR QIAEQFIQPF DLGTAPLLRA GLIKLAPERH LFMLDLHHIV
VDGVSIGLLI EEFAQLYHGE ELPALRIQYK DFAKWQQDWF QTEEFAEQEA YWLNTFTGEI
PVLNLPTDYP RPSVKSFAGD RFVFGSGTAL PKQLHQLAQE TGTTLYMVLL AAYNVLLSKY
SRQEDIIVGA PTAGRSHAET ESIVGMFVNT LALRNEPAGG KTFRDFLAEV KINTLGAFEH
QDYPLDELVD KLDMQRDLSR NPLFDTVFIL QNMEQKPFEM EQLTITPYSA EVKQAKFDLS
LEAYEENAEI IFSLDYSTKL FSRETIEKIA THFIQILRAV IAEPEMPLSE ITMLTEAEKQ
RLLVDFNGAH KDFPQNKTLQ ALFEEQAEKS PQATAVEISG QPLSYQELNE RANQLAATLR
ERGVQPDQPV GIMANRSVEM VVGILAILKA GGAYVPIDPE YPEERVAYML TDCQARLVLT
QKHLGAKLGS SVTAECLYLD DESNYGVHRS NLQPINTASD LAYIIYTSGT TGKPKGVMVE
HRGIVNNVLW KKAEYQMKVG DRSLLSLSFA FDAFVLSFFT PVLSGATVVL AEDEEAKDPV
SLKKLIAASR CTLMTGVPSL FQAILECSTP ADIRPLQTVT LGGEKITAQL VEKCKQLNPD
LVIVNEYGPT ESSVVATWQR LAGPDAAITI GRPIANTSLY IVNQYHQLQP IGVVGEICIG
GRGLARGYWN KPALTEEKFV SHPFAAGERM YKTGDLGKWL PDGTIEYIGR IDEQVKVRGY
RIEIGEIESA LLAAEKLTAA VVVVYEDQLG QSALAAYFTA DEQLDVTKLW SHLSKRLPSY
MIPAHFVQLD QLPLTPNGKV DKKALPKPEG KPVTEAQYVA PTNAVESKLA EIWERVLGVS
GIGILDNFFQ IGGHSLKAMA VAAQVHREYQ VELPLKVLFA QPTIKALAQY VATSGKETYV
PIEPAPLQEY YPVSSAQKRM YVLRQFADTG TVYNMPSALY IEGDLDRKRF EAAIHGLVER
HESLRTSFHT VNGEPVQRVH EHVELNVQYA EVTEAQVEPT VESFVQAFDL TKAPLLRVGL
FKLAAKRHLF LLDMHHIISD GVSAGIIMEE FSKLYRGEEL PALSVHYKDF AVWQSELFQS
DVYTEHENYW LNAFSGDIPV LNLPADFSRP LTQSFEGDCV SFQADKALLD DLHKLAQESQ
STLFMVLLAA YNVLLAKYSG QEDIVVGTPI AGRSHADIEN VLGMFVNTLA LRNYPVETKH
FQAFLEEVKQ NTLQAYAHQD YPFEALVEKL DIQRDLSRNP LFDTMFILQN LDQKAYELDG
LKLEAYPAQA GNAKFDLTLE AHEDETGIHF ALVYSTKLFQ RESIERMAGH FLQVLRQVVA
DQATALREIS LLSEEERRIV TVDFNNTFAA YPRDLTIQEL FEQQAAKTPE HAAVVMDGQM
LTYRELNEKA NQLAHVLRQN GVGKESIVGL LADRSLEMIT GIMGILKAGG AYLGLDPEHP
SERLAYMLED GGVKVVLVQK HLLPLVGEGL MPIVLEEESL RPEDCGNPAI VNGASDLAYV
MYTSGSTGKP KGVMVEHRNV TRLVMHTNYV QVRESDRMIQ TGAIGFDAMT FEIFGALLHG
ASLYLVSKDV LLDAEKLGDF LRTNQITTMW LTSPLFNQLS QDNPAMFDSL RALIVGGEAL
SPKHINRVKS ALPDLEIWNG YGPTENTTFS TCYLIEQHFE EQIPIGKPIA NSTAYIVDGN
NQPQPIGVPG ELCVGGDGVA RGYVNKPELT AEKFVPNPFA PGETMYRTGD LARWLPDGTI
EYLGRIDQQV KIRGYRIELG EIETVLSQQA QVKEAVVAVI EEANGQKALC AYFVPEQAVD
AAELREAMSK QLPGYMVPAY YVQMEKLPLT ANGKVDRRAL PQPSGERTTG SAFVAAQNDT
EAKLQQIWQE VLGIPAIGIH DNFFEIGGHS LKAMNVITQV HKTFQVELPL KALFATPTIH
ELAAHIAESA FEQFETIQPV EPAAFYPVSF AQKRMYILHQ FEGSGISYNV PSVLVLEGKL
DYDRFAAAIQ SLVKRHESLR TSFHSVNGEP LQRVHPDVEL PVRLLEATED QSESLIQELI
QPFDLEIAPL FRVNLIKLGA ERHLFFMDMH HIISDGVSLA VIVEEIASLY AGKQLSDLRI
QYKDFAVWQT KLAQSDRFQK QEDFWTRTFA GEIPLLNLPH DYPRPSVQSF DGDTVALGTG
HHLLEQLRKL AAETGTTLFM VLLAAYHVLL SKYAGQEEIV VGTPIAGRSH ADVERIVGMF
VNTLALKNTA AGSLSFRAFL EDVKQNALHA FEHQDYPFEH LVEKLQVRRD LSRNPLFDTM
FSLGLAESAE GEVADLKVSP YPVNGHIAKF DLSLDAMEKQ DGLLVQFSYC TKLFAKETVD
RLAAHYVQLL QTITADPDIE LARISVLSKA ETEHMLHSFL ATKTAYPTDK TFQKLFEEQV
EKTPNEIAVL FGNEQLTYQE LNAKANQLAR VLRRKGVKPE STVGILVDRS LYMVIGMLAV
LKAGGTFVPI DPDYPLERQA FMLEDSEAKL LLTLQKMNSQ VAFPYETFYL DTETVDQEET
GNLEHVAQPE NVAYIIYTSG TTGKPKGVVI EHRSYANVAF AWKDEYHLDS FPVRLLQMAS
FAFDVSTGDF ARALLTGGQL VICPNGVKMD PASLYETIRR HEITIFEATP ALIMPLMHYV
YENELDMSQM KLLILGADSC PAEDFKTLLA RFGQKMRIIN SYGVTEACID TSYYEETDVT
AIRSGTVPIG KPLPNMTMYV VDAHLNLQPV GVVGELCIGG AGVARGYLNR PELTEEKFVP
NPFAPGERLY RTGDLAKWRA DGNVEFLGRN DHQVKIRGVR IELGEIETQL RKLDGITEAV
VVAREDRGQE KELCAYVVAD HKLDTAELRA NLLKELPQAM IPAYFVTLDA LPLTANGKVD
RRSLPAPDVT MLRTTEYVAP RSVWEARLAQ VWEQVLNVPQ VGALDDFFAL GGHSLRAMRV
LSSMHNEYQV DIPLRILFEK PTIQELAAFI EETAKGNVFS IEPVQKQAYY PVSSAQKRMY
ILDQFEGVGI SYNMPSTMLI EGKLERTRVE AAFQRLIARH ESLRTSFAVV NGEPVQNIHE
DVPFALAYSE VTEQEARELV SSLVQPFDLE VAPLIRVSLL KIGEDRYVLF TDMHHSISDG
VSSGILLAEW VQLYQGDVLP ELRIQYKDFA VWQQEFSQSA AFHKQEAYWL QTFADDIPVL
NLPTDFTRPS TQSFAGDQCT IGAGKALTEG LHQLAQATGT TLYMVLLAAY NVLLAKYAGQ
EDIIVGTPIT GRSHADLEPI VGMFVNTLAM RNKPQREKTF SEFLQEVKQN ALDAYGHQDY
PFEELVEKLA IARDLSRNPL FDTVFTFQNS TEEVMTLPEC TLAPFMTDET GQHAKFDLTF
SATEEREEMT IGVEYSTSLF TRETMERFSR HFLTIAASIV QNPHIRLGEI DMLLPEEKQQ
ILAGFNDTAV SYALDKTLHQ LFEEQVDKTP DQAALLFSEQ SLTYSELNER ANRLARVLRA
KGVGPDRLVA IMAERSPEMV IGILGILKAG GAYVPVDPGY PQERIQYLLE DSNAALLLSQ
AHLLPLLAQV SSELPECLDL NAELDAGLSG SNLPAVNQPT DLAYVIYTSG TTGKPKGVMI
PHQGIVNCLQ WRRDEYGFGP SDKALQVFSF AFDGFVASLF APLLGGATCV LPQEAAAKDP
VALKKLMAAT EVTHYYGVPS LFQAILDCST TTDFNQLRCV TLGGEKLPVQ LVQKTKEKHP
AIEINNEYGP TENSVVTTIS RSIEAGQAIT IGRPLANVQV YIVDEQHHLQ PIGVVGELCI
GGAGLARGYL NKPELTAEKF VANPFRPGER MYKTGDLVKW RTDGTIEYIG RADEQVKVRG
YRIEIGEIES AVLAYQGIDQ AVVVARDDDA TAGSYLCAYF VAATAVSVSG LRSHLAKELP
AYMIPSYFVE LDQLPLSANG KVDRKALPKP QQSDATTREY VAPRNATEQQ LAAIWQEVLG
VEPIGITDQF FELGGHSLKA TLLIAKVYEY MQIELPLNLI FQYPTIEKVA DFITHKRFES
RYGTAILLNQ ETARNVFCFT PIGAQSVYYQ KLAAEIQGVS LYSFDFIQDD NRMEQYIAAI
TAIDPSGPYT LMGYSSGGNL AFEVAKELEE RGYGVTDIIL FDSYWKDKAI ERTVAETEND
IAQLFAEIGE NTEMFNMTQE DFQLYAANEF VKQSFVRKTV SYVMFHNNLV NTGMTTAAIH
LIQSELEADE EAPVAAKWNE SAWANATQRL LTYSGHGIHS RMLAGDYASQ NASILQNILQ
ELFILK
//