LGRD_BREPA
ID LGRD_BREPA Reviewed; 5085 AA.
AC Q70LM4;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Linear gramicidin synthase subunit D;
DE Includes:
DE RecName: Full=ATP-dependent D-leucine adenylase;
DE Short=D-LeuA;
DE AltName: Full=D-leucine activase;
DE Includes:
DE RecName: Full=Leucine racemase [ATP-hydrolyzing];
DE EC=5.1.1.-;
DE Includes:
DE RecName: Full=ATP-dependent tryptophan adenylase;
DE Short=TrpA;
DE AltName: Full=Tryptophan activase;
DE Includes:
DE RecName: Full=ATP-dependent glycine adenylase;
DE Short=GlyA;
DE AltName: Full=Glycine activase;
DE Includes:
DE RecName: Full=Linear gramicidin--PCP reductase;
DE EC=1.-.-.-;
GN Name=lgrD;
OS Brevibacillus parabrevis.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Paenibacillaceae; Brevibacillus.
OX NCBI_TaxID=54914;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 8185 / DSM 362 / JCM 20017 / NBRC 3331 / NCDO 717 / NCIMB 8598
RC / IAM 1031;
RX PubMed=14670971; DOI=10.1074/jbc.m309658200;
RA Kessler N., Schuhmann H., Morneweg S., Linne U., Marahiel M.A.;
RT "The linear pentadecapeptide gramicidin is assembled by four multimodular
RT nonribosomal peptide synthetases that comprise 16 modules with 57 catalytic
RT domains.";
RL J. Biol. Chem. 279:7413-7419(2004).
RN [2]
RP CHARACTERIZATION OF REDUCTASE ACTIVITY.
RC STRAIN=ATCC 8185 / DSM 362 / JCM 20017 / NBRC 3331 / NCDO 717 / NCIMB 8598
RC / IAM 1031;
RX PubMed=15938641; DOI=10.1021/bi050074t;
RA Schracke N., Linne U., Mahlert C., Marahiel M.A.;
RT "Synthesis of linear gramicidin requires the cooperation of two independent
RT reductases.";
RL Biochemistry 44:8507-8513(2005).
CC -!- FUNCTION: Activates the 13th to the 16th (Trp, D-Leu, Trp and Gly)
CC amino acids in linear gramicidin and catalyzes the formation of the
CC peptide bond between them. This enzyme is also responsible for the
CC epimerization of the 14th (D-Leu) amino acid. It also catalyzes the
CC NAD(P)H-dependent reduction of the C-terminal glycine residue of the N-
CC formylated 16-mer peptide, that binds to the peptidyl carrier domain of
CC the terminal module of this protein, to form a peptidyl-aldehyde
CC intermediate that is released from the enzyme complex.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305};
CC Note=Binds 4 phosphopantetheines covalently. {ECO:0000305};
CC -!- SUBUNIT: Large multienzyme complex composed of 4 subunits; LgrA, LgrB,
CC LgrC and LgrD.
CC -!- DOMAIN: Four module-bearing peptide synthase with a C-terminal
CC epimerization domain. Each module incorporates one amino acid into the
CC peptide product and can be further subdivided into domains responsible
CC for substrate adenylation, thiolation, condensation (not for the
CC initiation module), and epimerization (optional). Contains a reductase
CC domain at the C-terminus.
CC -!- MISCELLANEOUS: Linear gramicidin is a pentadecapeptide antibiotic
CC produced during sporulation.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AJ566197; CAD92852.1; -; Genomic_DNA.
DR SMR; Q70LM4; -.
DR STRING; 54914.AV540_01950; -.
DR PRIDE; Q70LM4; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase 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 GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR CDD; cd05235; SDR_e1; 1.
DR Gene3D; 1.10.1200.10; -; 4.
DR Gene3D; 3.30.300.30; -; 4.
DR Gene3D; 3.30.559.10; -; 5.
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; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR010060; NRPS_synth.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR Pfam; PF00501; AMP-binding; 4.
DR Pfam; PF13193; AMP-binding_C; 4.
DR Pfam; PF00668; Condensation; 5.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 4.
DR SMART; SM00823; PKS_PP; 4.
DR SUPFAM; SSF47336; SSF47336; 4.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 4.
DR TIGRFAMs; TIGR01720; NRPS-para261; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
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; Isomerase; Ligase; Multifunctional enzyme; NAD;
KW NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Repeat.
FT CHAIN 1..5085
FT /note="Linear gramicidin synthase subunit D"
FT /id="PRO_0000193092"
FT DOMAIN 962..1037
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2023..2097
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3544..3619
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4601..4676
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 997
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2058
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3579
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4636
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 5085 AA; 567458 MW; 8E0618C4AC39BF24 CRC64;
MNNIETYYPV TPLQQGLIFH SLLEPESGAY IVQMGLKLQG PLNIPLFEQA WQCLVDRHAI
FRTRFVGGKV KEYVQVVLKD LKISLVEHDL IHLSSSEQEA FLHHFAKEDR KRGFDIEQAP
LMRLNVFHLN SETVHFLWTL HHVLIDGWSM PLVFGEVFAA YEMLSKGQPL SLPPVRAYRD
YIVWLKKQDL QQAEAFWRTY MQGFTEATPL SFGRAYKNPY LDQKQYRELD LTVSEQTSKA
LQTLARQHRL TVNTIVQGAW ALLLNRYSGQ DDIVFGATVS GRPADLPGVE TMIGLFINTL
PVRVQVNAEE SVINWLKTLQ QQQADFRQYE YTPLVEIQGW SDVPRGQSLF ESILVFENMP
VGKSGGGESA ISIVDVYSEE QTNYPFTLVA ASGKTIDIKV KFDESQFELA AIERVVDQLH
SLLSSIAKNA KQRIGDLSLI SESERQQVLV EWNQTAEDYP SGLCIHQAFE QQAEKTPDAV
AVAYKNRELT YAQLNERANQ LAHRLIRKGV KPDTLVGICL ERSPEMIIGI LGVMKAGAAY
VPIDPAHPQE RIAYMVADSQ ASALLTQQSL LEILPVTAAH VICLDSDLLA DEPVDNASSE
VTEQNLAYVI YTSGSTGLPK GVMIEHHSAI NLAYALIDAF DIQPTSRVLQ FTSFSFDVSV
SEVVMALLAG ATLVIEDRES LLPGPELIQV LQEQRITTVS MVSSVLAALP DADLPDLHTL
IVGGEAPSRE LVARYAPGRQ FFNCYGPTEA TVCSTMMLCQ AGMNNPPIGR PIANATVYVL
DANLNPVPVG VPGELYIGGK GLARGYWNRP ELTAESFIPH PFGTAGERLY RTGDLVRYRQ
DGNLEFLGRI DHQVKIRGYR IELGEIENAI RQHPAVQEAV VIAREEKAGD KRLAAYLVAA
GKAQPPAEEI ALFLKETLPE YMVPAGVVWL DAIPLTVNGK VDRRALPVPD WGQLSTKREY
VAPRTPTEEM VANIWSQVLS VERVGSFDDF FELGGHSLLA TQTVSRLKEA FGVDLPLRVL
FECSTVNKLS EWIAAAGEDK SGLSRIPLVP VSRDRHLPLS FAQQRLWFFD RLMPNSALYN
IPTAVRLQGE LDMDALEQSL QTIIQRHESL RTTFTDHNGE AVSVIHPEID WKLERIDLRE
RSEEMRNEAG LRLAKEEANR PFDLVTGPLM RATIIQTDER DFIFLLNVHH IIADGWSAGI
LIRELFHCYQ AFAKAEAPQL AELPIQYADY AYWQREWLTS DVLDEQLSYW RAKLGGAEPL
LALPTDRPRP AVQSYAGSSI SLLFDDELRA NLLALSKREG TTLFMTLLAA FQVFLYRYTG
QDDILVGTPE AGRSRQETEG LIGFFINTLV MRTDLSGEPS FKEVLARVRE TALGAYAHQD
LPFEKLVDEL NVERSLSYSP LFQVMFVLQN IPVQADALDG IRILPLEGSQ QVETTKFDLT
LTMAEAANGL AATFEYNTAL FERNTVERMI GHFSSLLKAV AANANQAITA LPLMSEVEEQ
QLVLEWNDTA VAYSTEQLVH ELVAQVARDM PDQPAVVTRD QLLTYGQLEA KANQLAHYLQ
KQGVGRGSLV GICVERSVEM VIGQLAIMKA GAAYIPMDPA YPKERLAFMM HDASMAIVLT
QAKLRQKLPA DTSRLICLDA DWETIAQEPT AALVNTTAAS DLAYVIYTSG STGTPKGVEI
EHAALLNLIF WHQRAYDVTA TDRASQIAGT AFDASVWEIW PYVTKGATLY LPEEEIRLVP
EKLRDWLVAS NITVSFLPTP LTESMLALEW PGDTALRYML TGGDKLHHYP SEKIPFTLVN
QYGPTENTVV ATAGIVPKEA GQTAAPTIGR PIDNVQVYIL DAHRQPVPVG VSGELYIGGS
SLARGYLNRP DLTQERFVAH PFTEKAGARL YRTGDLVRSL PDGSIEFIGR ADDQTSIRGF
RVELGEVETA IVALPAVKEA VVTVCTDKQG TKRLAAYLVL EEGAALATGD IRKALKETLP
DYMVPAFFTQ LAYLPLTPNG KVDRKNLPAP DFQRPELEGE FVSPSTEKER RLAAIWKDVL
GIEQIGIHDN FFELGGDSIL SIQIVSRANQ AGLSLAPKQL FEYQTIAELA EIVEEKAAVQ
AEQGAVTGEL PLLPIQKWFF RLPLANRDHW NQSVLLSIQA GIDPAALKQA VGQLMFQHDA
FRMRYTQSES GWLQAMDAPS ETIPFRVEDL SQLAPEEQSS AIEAIANETQ TQLSLRAGQV
VQTIYFHLGK EVPGRLLIVA HHLVVDGVSW RIILEDLQHA YQQIAAGQEV KLPAKTTSYK
EWAQELERYA HSEAFKHEKS YWLSKSSVHS TELPADMPDS AENTEATVKS VHFSLTVEET
KALLQQVPQA YRTQINDVLL AALAKALGQW TGKRSVFVNV EGHGREELAE HLDLSRTVGW
FTSMYPVHLQ WDETFSVRRA LLTTKEELRA IPNKGLGYGV LRYLHAEQEI VDAISRIQAD
VLFNYMGKID QIVGSDSLFG SAPESSGANL CPSAQRHHLL DVNSVVAGEQ LHVTWRYSEK
LQRESTIAAV AESFMAALRE IVAHCTLPEA GGYSPSDFPL AVLEQKQIDK HIGFDRQIED
VYTLSPLQQG MLFHSLYNQD SGDYVVQFAV TFQNLDVSVL EKAWQNVLDR HSILRTHFVW
EGLSEPHQVV RKDVKVTLTK EDWRHLQADV QDEMLAAFLE EDRRRSFDIA QAPLSRWVVF
QTKDEEYRFV WSFHHVLLDG WSVPIVLNEL LAHYAAISEG REGKLVPSQP FSQYIAWLKR
QDREKAKPFW TDQLKGFHEP TSLGMGKNVA ASQQKQYKEQ SVLLSEEATE HLQSFTREHQ
LTLNTLVQGA WGWILGSYSG EEEVLFGATG SGRPADLPGV ETMVGSFINT LPVRVPLQTD
ATLLAWLKDL QRRQLEIREY EYTPLFDIQG WSELPRGSAL FESILVFENY PTVQAAKKGE
DEAASATSGV SLEIHDVAAV EQTNYPLTLV AAPGKQVAFK LKYDQDRFDD AMIERVLNQM
TRLMVYMSKS PELRLNDVAL MDEDERKQVL IDWNRTEKEY PRELCLHHAF EQQAAKTPEN
IALEYKEQSL SYAGLNERAN QLAHLLIAQG VKPDTTVAIC VERSMEMIIG ILGVLKAGAA
YVPIDPAHPE ERIAYMLDDS QAVVVLTQAG LADKFTQAAA PVICLGEKLF ADRAHVDVDN
IQTDVASTNL AYVIYTSGTT GLPKGVAVEH RSAMNMVQAY IAYFGLDESS RVLQFTSFSF
DVSVSEIWQA LLSGGTLVIE DRESLLPGPD LVRTLRERRI SKVSMASSLL ASLPVAEYPD
LAVLEVGGDA CSRELVARYA TGRKFFNCYG PTEATVGTVI KQLTLDDDTP TIGRPFPNTK
LYVLDQNRKP VPVGVPGELY IGGECLARGY WNRPELTAER FVANPFGQPG ERLYRTGDLV
RYLPDGNVDY LGRFDDQVKI RGYRIELGEI AEALRQHAAI REAVVLAREV RPGDKRLAAY
LTSAAEQELS VDEIKQWLKE KLPDYMVPAS YTWLPAIPLN VNGKVDRKAL PAPDWGQITA
AYVAPRNPLE EMIANVFAEV LAVEKVGIDD NFFELGGHSL LATQTVSRLR EIVGVELQLR
TLFEHPTVAG LGEQLELLTK QSSRKLAPPI GKVSRKEPLP LSFTQQRLWF LEQFTQNSSI
NNIPSFLRIQ GELDVAAWEA SFSAIILRHE SLRTSFEVRD GRPVQVIQPH GDWAMTRIDL
RALEPAEREA EIKRLAEQAI VQPFDLTKGL LLRASLVQLD ANDFVFLFVM HHIASDGWSM
GILLSELMTN YKAFRQGEAS PLGELPIQYA DFAVWQREWL SGEVLAEQLG YWREKLKGSE
PLLQLPTDRP RPPVQTYEGE KMSVQFGAEL LKQLQSLSRK EGATLFMTLF AAFQTLLYRY
TNQDDILVGT PIAGRNKQET EQLIGYFINT LVLRTDMSGH PSFRELLARV RETALEAYAH
QDVPFEKLLD ELQLERSMSY SPLFQVMFIL QNIPVQAEPA GDIQLSSFDL ELGAVTSKFD
MTVTMVETPD GLLATLEYNK ALFDSSTITR MVEHFHKLME EIVANPDQSI TLLPLMREEE
EQLLITEWNR TEVPYSREKC VHEMIEEMVS KAPDSIALIV GEQRVTYGEL NRQANQLAHY
LRKQGVGPEV LVGICAERTV EMMIGLLAIL KAGGAYVPID PAYPAERIAY IIGHSQIPVL
LTQEHLLPTL PEHQAKVICL DRDWATVAVE SEENPGKLAT SDNLIYVIYT SGSTGNPKGV
ALEHRSVIYF LSWAHDTYTP EEMSGVLFST SICFDLSVYE MFATLTMGGK VIMAENALQL
PALPAADQVT LVNTVPSAAT ELVRMKGIPA SVRVINLCGE PLSNRLAQEL YAFPHVEKVF
NLYGPTEDTV YSTHAIVTKG ATNEPLIGRP QFNTHVFVLD SHRKPVPVGV PGELYLSGSG
LARGYLHRPD LTAERFVQNP FREPGARMYR TGDLVRYLPD GNLQFVGRVD YQVKIRGYRI
ELGEIESVLN RFPGVKEVVL LAREDREGDK CLVAYIVFEA DCTSKIHDLN HFLADKLPAY
MIPQHYMILD SLPKTPNGKL DRKALPKPEY DRSEAGVEYV APQTPVEIML HAHWAAVLEM
ETIGVHDNFF EIGGHSLLAT QLIFKVREEL QLEVPLRILF ETPTIAGMAK TIEEIIKHGL
TSVSQEIDAK GLQDEVALDP AILAEQPYEG DPSQFQAALL TGATGFLGAF LLRDLLQMTD
ADIYCLVRAS GEEEGLARLR KTLQLYELWD EAQAHRIIPV IGDLAQPRLG LSAGQFDALA
ATVDVIYHNG ALVNFVYPYA ALKKANVIGT EEIIRLAAAK KTKPVHFVST IFTFASEEGE
ESVAVREEDM PENSRILTSG YTQSKWVAEH IVNLARQRGI PTAIYRCGRM TGDSETGACQ
KDDLMWRIAA GIIDLGKAPD MSGDLDMMPV DFASKGIVHL SMTEHSVNSN FHLLNPNATD
YDDLIAAIEN KGFELERVTM DEWIEAVQED AKDKGMDANS AAPLGNLFSD GHSSRGSVVY
VGNKTTRLLR QADIECPEID EEVFAKVLDY FARTGQLRVT QNTRN
