ACVS_AMYLA
ID ACVS_AMYLA Reviewed; 3649 AA.
AC P27743;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase;
DE EC=6.3.2.26;
DE AltName: Full=Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase;
DE Short=ACV synthetase;
DE Short=ACVS;
GN Name=pcbAB;
OS Amycolatopsis lactamdurans (Nocardia lactamdurans).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Amycolatopsis.
OX NCBI_TaxID=1913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=VAR LC 411;
RX PubMed=1956290; DOI=10.1111/j.1365-2958.1991.tb01885.x;
RA Coque J.J.R., Martin J.F., Calzada J.G., Liras P.;
RT "The cephamycin biosynthetic genes pcbAB, encoding a large multidomain
RT peptide synthetase, and pcbC of Nocardia lactamdurans are clustered
RT together in an organization different from the same genes in Acremonium
RT chrysogenum and Penicillium chrysogenum.";
RL Mol. Microbiol. 5:1125-1133(1991).
CC -!- FUNCTION: Each of the constituent amino acids of the tripeptide acv are
CC activated as aminoacyl-adenylates with peptide bonds formed through the
CC participation of amino acid thioester intermediates.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 ATP + H2O + L-2-aminoadipate + L-cysteine + L-valine = 3 AMP
CC + 3 diphosphate + 3 H(+) + N-[(5S)-5-amino-5-carboxypentanoyl]-L-
CC cysteinyl-D-valine; Xref=Rhea:RHEA:23196, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:35235, ChEBI:CHEBI:57762, ChEBI:CHEBI:58572,
CC ChEBI:CHEBI:58672, ChEBI:CHEBI:456215; EC=6.3.2.26;
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Note=Binds 3 phosphopantetheines covalently.;
CC -!- PATHWAY: Antibiotic biosynthesis; penicillin G biosynthesis; penicillin
CC G from L-alpha-aminoadipate and L-cysteine and L-valine: step 1/3.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X57310; CAA40561.1; -; Genomic_DNA.
DR PIR; S18268; S18268.
DR SMR; P27743; -.
DR ESTHER; nocla-acvs; Thioesterase.
DR UniPathway; UPA00149; UER00239.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050564; F:N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase activity; IEA:UniProtKB-EC.
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:0008610; P:lipid biosynthetic 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 Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 3.
DR Gene3D; 3.40.50.12780; -; 1.
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; IPR042099; ANL_N_sf.
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; 3.
DR Pfam; PF13193; AMP-binding_C; 3.
DR Pfam; PF00668; Condensation; 3.
DR Pfam; PF00550; PP-binding; 3.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR SUPFAM; SSF53474; SSF53474; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 3.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; ATP-binding; Ligase; Multifunctional enzyme;
KW Nucleotide-binding; Phosphopantetheine; Phosphoprotein; Repeat.
FT CHAIN 1..3649
FT /note="N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine
FT synthase"
FT /id="PRO_0000193059"
FT DOMAIN 783..860
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1859..1936
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2909..2984
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 401..861
FT /note="Domain 1 (adipate-activating)"
FT REGION 1014..1937
FT /note="Domain 2 (cysteine-activating)"
FT REGION 2079..2985
FT /note="Domain 3 (valine-activating)"
FT ACT_SITE 3502
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250"
FT MOD_RES 820
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1896
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2944
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3649 AA; 404088 MW; 6FD095704F858E6B CRC64;
MTSARHLKSA ADWCARIDAI AGQRCDLEML LKDEWRHRVA VRDSDTAVRA TQEKELTISG
QDYTALKQAL GAMPLEAFAL ATLHSVLHAY GHGHQTVVAF LRDGKVLPVV VDHLEQAGLT
CAEAAEQLED AVAREDMYLP PEELLQRGLF DALLVLADGH LGFTELPPAP LVTIVRDDPA
AGCLHWRIAY AGEFFEDKII AGVLDVAREV LGQFIGRPEQ LVADIDLVSA EQELQLHQWN
GTDGEFDEDK RLNELFEDVV RRAPDREAVV CGDVRLTYRE VNERANQFAH WLIQGPVRVR
PGALIGLYLD KSDLGVVATF GIWKSGAAYV PIDPAYPAER IRFLVGDTGL SGIVTNRRHA
ERLREVLGDE HASVHVIEVE AVVAGPHPEQ ARENPGLALS SRDRAYVTYT SGTTGVPKGV
PKYHYSVVNS ITDLSERYDM RRPGTERVAL FASYVFEPHL RQTLIALINE QTLVIVPDDV
RLDPDLFPEY IERHGVTYLN ATGSVLQHFD LRRCASLKRL LLVGEELTAS GLRQLREKFA
GRVVNEYAFT EAAFVTAVKE FGPGVTERRD RSIGRPLRNV KWYVLSQGLK QLPIGAIGEL
YIGGCGVAPG YLNRDDLTAE RFTANPFQTE EEKARGRNGR LYRTGDLARV LLNGEVEFMG
RADFQLKLNG VRVEPGEIEA QATEFPGVKK CVVVAKENAT GDRHLVGYYL VEDGAEVAEA
DLIAFLEQRL IRIMVPARMV RLTSIPVNVN GKVDWRALPD VSLHPAPANA MNGALLAIDG
SNAPLLAITE QLRAIWSEVL GVPQNRIGER DDFFRLGGQS ISCILLIARV RQRLSLSLGV
EDVFALRTLD ALAGHLESQG HAEPEVVAEE VTTGSEPVRV LANGLQQGLL YHHLKTAGGD
DAYVVQSVHR YHAPIRPELM KDAWQAARQT YPALRLRFDW AEEPVQIVDN DDKPFDWRFV
DLSATADDAE QEARVRELQE RDRTEPYDLA GGRLFRVYLI KQREDLFSLI FSCHHIILDG
WSLPVLHDEV HRNYLALRAG QPIESDVDNA YVAAQRYWEA HRNDHAAYWV EQLGRIDERG
DFAGLLNEKS RYRVSLGDYD HVQRHRTRKL YLGADLTGAL KAGCAADQVT LHSVLQFVWH
KVLHAIGGGN TTVVGTIVSG RNLPVDGIEN SAGLFINTLP LIVDHDQQAG QNVAEAVRDI
QAAVNTMNSK SIVELGRLQS GEMKRRLFDT LLVLENYPRL LDEEEELAHQ EALRFEKAYD
ADKVDYPIAV VAREEGDELT VTLWYAGELF DEDTIDTLLD VARTLFRQVT EDIARPVREL
DLISPSMRAR FDSWNETAEE FPADKTLHAV FEEMAERWPD EIAVVYRENR LTYRELNERA
NRLAHYLRSV VELRPDDLVA LVLDKSELMI TAIIAAWKTG AAYVPIDSGY PDDRISFMLS
DTAARVVVTN EIHSDRLRSL AETGTPVLEI ELLHLDDQPA VNPVTETTST DLAYAIYTSG
TTGKPKAVLV EHRGVVNLQV SLAKLFGLDK AHRDEALLSF SNYIFDHFVE QMTDALLNGQ
KLVVLDDSMR TDPGRLCRYM NDEQVTYLSG TPSVLSLYDY SSATSLTRID AIGEDFTEPV
FAKIRGTFPG LIINGYGPTE ISITSHKRPY PPDVHRVNKS IGFPVANTKC HVLNKAMKPV
PVGGIGELYI GGIGVTRGYL NREDLTADRF VENPFQTAEE RRLGENGRLY KTGDLVRWLP
NGEVEYLGRT DLQVKIRGQR VELGEVEAAL SSYPGVVRSL VVAREHAVGQ KYLVGFYVGE
QEFDEQDLKQ WMRKKLPESV VPARVLRITD IPVTPSGKLD ARRLPETDFG AGEGAEYVAP
VSEFELKLCG IWAQVLEIAP DRIGVHDDFF ALGGDSIRAM ALAQAITTGF GQGLGVATVL
QHTTLAAQAE HIQAAALEHT AWTPPPTAVE HPPVSLAQER LLFIDDFEGG TAAYNIPFVL
RLPAHTRAAL PGALGTLVRR HPALRTLLKT DDQGVRRQYP IPADDVRLEV PSTTVDSRAE
LDEVLTERAG YVFRLHEELP IRAEAFDHGD EIYLSVVVHH SCFDGWSWDI FRRELAALLD
GVPEADLGAL RGTYGEFAVW QRQYLTGKRL AALTEFWTGA LGGFETIALP LDHPRPPRFD
YRGRELEFEL DERTTEALRE LARTARVSLY SVLLGAWCLM LNMYTGQHDL VVGTPSANRG
RPEFDRAVGF FANLLALRVR VDPAATLPAY VRSVGEAVVA AQVHGELPFE QLVKELKVEK
DPSRHPILQL NFTLQNVSDH TSALTGYQPD SGGWTTTKFD LSATMTETAT GLAGNLTYAA
SLFDDTSASG FIATFKHVLA EFASAAAQTP IAQLTALDEP GQAALPDATR RARRPGGPGR
CTRLFEEVAA TWPDRVAVVH GDVRLTYREL NERANRLAHH LRSVAEPRAD ELIALVLDKS
ELTLVAILAV WKAGAAYMPI DPSYPDDRIA FMLSDTGAKL VLAGEAHGSR VRGLTSGDVL
DLEQLDLTGE PAENPVTETT STELAYAIYT SGTTGKPKAV LVSHGSVDSF RAQLSGRYFG
SPDESAEAVL FLANYVFDFS VEQLALSVLG GHKLLVPPPS AADDPAFYEL ANREGLSYLS
GTPTQVERFD LARLSHLRCV LVAGEAFQPQ HFEKMRGEFA GPILNAYGTT ETTVYNTVHR
FEPGDAYRNT LGAPLGNTRL YVLGDGMKLL PTGAVGELYL AGDCVTEGYL HRPELTRERF
LPNPFAAESG RFPMIYRTGD VVRRGPDGEL QYLGRNDAQV KINGLRIEPG EVEAALAGCS
GVRQCAVVAG ADPQAPERKR LVGYYLPEPG AAVDEADLFA ALRAQLMPSM VPSLLVRLDR
PLPMTITGKL DVDALPSADF SPKRAAYAAP RDRVEARLCH LWSAQLPGGT VGIDDDFFRC
GGDSISALHL ASQVQREIER KVSVKYLFDH PTVRSFVDNV LSGLAESSGD DEPEQGRLTG
ECPMLPIQEW FFAKPLADRH RWNHNFAIRT PPLDPGELRT ALDRLVEHHD AFRLRFPESG
GEVYAEDAAP ITLHELDVRG LADADLRQRL VDWQRTFDLA NGPTACAAYL HGFDDGTARV
WFALHHLVVD TVSWHILAQD LEILYNGGDL GAKTGSYRQW AQAVRDYTPA EGEREFWAET
TRDMESAELL AQTEGTTRRR EEFALTAPDT RTLLAESPWA YDTEVNDLLL TATGFALRSI
TRQATNHLTV EGHGRELFEG APDVRDTVGW FTTMHPFAVE VDPGDLGRSV LATRANRRRV
PHHGIGYGAL FGGEAPLPAV SFNYLGRLGE GDGQPTEAWQ LDPALSGSHT VDGNRLANRS
SIDVTMSCTG GRLVAVVDSL LGEAATRLFA SELKVWLERL VSHTATVARN EPAREATTEL
FDPYILVNED AERTLFVLPP GEGGAESYLS NLARQLPDLR LVLFNNVHLH TPMGSFEELG
RYYVEHIRRL QPSGPYHLLG WSFGGVLSLE ISRQLARAGE RIDDLLLIDP YFGMRQASAN
IGLPGVEDIL DPINYHYRPD EADLARLAGR LGNLVLFKAG EPNDVVNGPH QPRLFEYYHG
TRFNHLDLLL PAAAIEVCDL AGETHHSWVR NEKLVRLMCE RISTSLGSD
