Reviewed, UniProtKB/Swiss-Prot P27743 (ACVS_NOCLA)

Names and origin

Protein names

Recommended name:
    N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
    EC=6.3.2.26
Alternative name(s):
    Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase
      Short name=ACV synthetase
      Short name=ACVS

Gene names

Name:

pcbAB

Organism

Nocardia lactamdurans

Taxonomic identifier

1913 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Pseudonocardineae › Pseudonocardiaceae › Amycolatopsis

Protein attributes

Sequence length	3649 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	Each of the constituent amino acids of the tripeptide acv are activated as aminoacyl-adenylates with peptide bonds formed through the participation of amino acid thioester intermediates.
Catalytic activity	L-2-aminohexanedioate + L-cysteine + L-valine + 3 ATP + H2O = N-(L-5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine + 3 AMP + 3 diphosphate.
Cofactor	Binds 3 phosphopantetheines covalently.
Pathway	Antibiotic biosynthesis; penicillin G biosynthesis; penicillin G from L-alpha-aminoadipate and L-cysteine and L-valine: step 1/3.
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family. Contains 3 acyl carrier domains.

Ontologies

Keywords
Biological process	Antibiotic biosynthesis
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding Phosphopantetheine
Molecular function	Ligase
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	antibiotic biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase activity Inferred from electronic annotation. Source: EC acyl carrier activity Inferred from electronic annotation. Source: InterPro cofactor binding Inferred from electronic annotation. Source: InterPro hydrolase activity, acting on ester bonds Inferred from electronic annotation. Source: InterPro phosphopantetheine binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 3649	3649	N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase		PRO_0000193059
Regions
	Domain	788 – 857	70	Acyl carrier 1
	Domain	1864 – 1933	70	Acyl carrier 2
	Domain	2910 – 2981	72	Acyl carrier 3
	Region	401 – 861	461	Domain 1 (adipate-activating)
	Region	1014 – 1937	924	Domain 2 (cysteine-activating)
	Region	2079 – 2985	907	Domain 3 (valine-activating)
Sites
	Active site	3502	1	For thioesterase activity By similarity
Amino acid modifications
	Modified residue	820	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	1896	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	2944	1	O-(pantetheine 4'-phosphoryl)serine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P27743-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 6FD095704F858E6B	FASTA	3,649	404,088
	10 20 30 40 50 60 MTSARHLKSA ADWCARIDAI AGQRCDLEML LKDEWRHRVA VRDSDTAVRA TQEKELTISG 70 80 90 100 110 120 QDYTALKQAL GAMPLEAFAL ATLHSVLHAY GHGHQTVVAF LRDGKVLPVV VDHLEQAGLT 130 140 150 160 170 180 CAEAAEQLED AVAREDMYLP PEELLQRGLF DALLVLADGH LGFTELPPAP LVTIVRDDPA 190 200 210 220 230 240 AGCLHWRIAY AGEFFEDKII AGVLDVAREV LGQFIGRPEQ LVADIDLVSA EQELQLHQWN 250 260 270 280 290 300 GTDGEFDEDK RLNELFEDVV RRAPDREAVV CGDVRLTYRE VNERANQFAH WLIQGPVRVR 310 320 330 340 350 360 PGALIGLYLD KSDLGVVATF GIWKSGAAYV PIDPAYPAER IRFLVGDTGL SGIVTNRRHA 370 380 390 400 410 420 ERLREVLGDE HASVHVIEVE AVVAGPHPEQ ARENPGLALS SRDRAYVTYT SGTTGVPKGV 430 440 450 460 470 480 PKYHYSVVNS ITDLSERYDM RRPGTERVAL FASYVFEPHL RQTLIALINE QTLVIVPDDV 490 500 510 520 530 540 RLDPDLFPEY IERHGVTYLN ATGSVLQHFD LRRCASLKRL LLVGEELTAS GLRQLREKFA 550 560 570 580 590 600 GRVVNEYAFT EAAFVTAVKE FGPGVTERRD RSIGRPLRNV KWYVLSQGLK QLPIGAIGEL 610 620 630 640 650 660 YIGGCGVAPG YLNRDDLTAE RFTANPFQTE EEKARGRNGR LYRTGDLARV LLNGEVEFMG 670 680 690 700 710 720 RADFQLKLNG VRVEPGEIEA QATEFPGVKK CVVVAKENAT GDRHLVGYYL VEDGAEVAEA 730 740 750 760 770 780 DLIAFLEQRL IRIMVPARMV RLTSIPVNVN GKVDWRALPD VSLHPAPANA MNGALLAIDG 790 800 810 820 830 840 SNAPLLAITE QLRAIWSEVL GVPQNRIGER DDFFRLGGQS ISCILLIARV RQRLSLSLGV 850 860 870 880 890 900 EDVFALRTLD ALAGHLESQG HAEPEVVAEE VTTGSEPVRV LANGLQQGLL YHHLKTAGGD 910 920 930 940 950 960 DAYVVQSVHR YHAPIRPELM KDAWQAARQT YPALRLRFDW AEEPVQIVDN DDKPFDWRFV 970 980 990 1000 1010 1020 DLSATADDAE QEARVRELQE RDRTEPYDLA GGRLFRVYLI KQREDLFSLI FSCHHIILDG 1030 1040 1050 1060 1070 1080 WSLPVLHDEV HRNYLALRAG QPIESDVDNA YVAAQRYWEA HRNDHAAYWV EQLGRIDERG 1090 1100 1110 1120 1130 1140 DFAGLLNEKS RYRVSLGDYD HVQRHRTRKL YLGADLTGAL KAGCAADQVT LHSVLQFVWH 1150 1160 1170 1180 1190 1200 KVLHAIGGGN TTVVGTIVSG RNLPVDGIEN SAGLFINTLP LIVDHDQQAG QNVAEAVRDI 1210 1220 1230 1240 1250 1260 QAAVNTMNSK SIVELGRLQS GEMKRRLFDT LLVLENYPRL LDEEEELAHQ EALRFEKAYD 1270 1280 1290 1300 1310 1320 ADKVDYPIAV VAREEGDELT VTLWYAGELF DEDTIDTLLD VARTLFRQVT EDIARPVREL 1330 1340 1350 1360 1370 1380 DLISPSMRAR FDSWNETAEE FPADKTLHAV FEEMAERWPD EIAVVYRENR LTYRELNERA 1390 1400 1410 1420 1430 1440 NRLAHYLRSV VELRPDDLVA LVLDKSELMI TAIIAAWKTG AAYVPIDSGY PDDRISFMLS 1450 1460 1470 1480 1490 1500 DTAARVVVTN EIHSDRLRSL AETGTPVLEI ELLHLDDQPA VNPVTETTST DLAYAIYTSG 1510 1520 1530 1540 1550 1560 TTGKPKAVLV EHRGVVNLQV SLAKLFGLDK AHRDEALLSF SNYIFDHFVE QMTDALLNGQ 1570 1580 1590 1600 1610 1620 KLVVLDDSMR TDPGRLCRYM NDEQVTYLSG TPSVLSLYDY SSATSLTRID AIGEDFTEPV 1630 1640 1650 1660 1670 1680 FAKIRGTFPG LIINGYGPTE ISITSHKRPY PPDVHRVNKS IGFPVANTKC HVLNKAMKPV 1690 1700 1710 1720 1730 1740 PVGGIGELYI GGIGVTRGYL NREDLTADRF VENPFQTAEE RRLGENGRLY KTGDLVRWLP 1750 1760 1770 1780 1790 1800 NGEVEYLGRT DLQVKIRGQR VELGEVEAAL SSYPGVVRSL VVAREHAVGQ KYLVGFYVGE 1810 1820 1830 1840 1850 1860 QEFDEQDLKQ WMRKKLPESV VPARVLRITD IPVTPSGKLD ARRLPETDFG AGEGAEYVAP 1870 1880 1890 1900 1910 1920 VSEFELKLCG IWAQVLEIAP DRIGVHDDFF ALGGDSIRAM ALAQAITTGF GQGLGVATVL 1930 1940 1950 1960 1970 1980 QHTTLAAQAE HIQAAALEHT AWTPPPTAVE HPPVSLAQER LLFIDDFEGG TAAYNIPFVL 1990 2000 2010 2020 2030 2040 RLPAHTRAAL PGALGTLVRR HPALRTLLKT DDQGVRRQYP IPADDVRLEV PSTTVDSRAE 2050 2060 2070 2080 2090 2100 LDEVLTERAG YVFRLHEELP IRAEAFDHGD EIYLSVVVHH SCFDGWSWDI FRRELAALLD 2110 2120 2130 2140 2150 2160 GVPEADLGAL RGTYGEFAVW QRQYLTGKRL AALTEFWTGA LGGFETIALP LDHPRPPRFD 2170 2180 2190 2200 2210 2220 YRGRELEFEL DERTTEALRE LARTARVSLY SVLLGAWCLM LNMYTGQHDL VVGTPSANRG 2230 2240 2250 2260 2270 2280 RPEFDRAVGF FANLLALRVR VDPAATLPAY VRSVGEAVVA AQVHGELPFE QLVKELKVEK 2290 2300 2310 2320 2330 2340 DPSRHPILQL NFTLQNVSDH TSALTGYQPD SGGWTTTKFD LSATMTETAT GLAGNLTYAA 2350 2360 2370 2380 2390 2400 SLFDDTSASG FIATFKHVLA EFASAAAQTP IAQLTALDEP GQAALPDATR RARRPGGPGR 2410 2420 2430 2440 2450 2460 CTRLFEEVAA TWPDRVAVVH GDVRLTYREL NERANRLAHH LRSVAEPRAD ELIALVLDKS 2470 2480 2490 2500 2510 2520 ELTLVAILAV WKAGAAYMPI DPSYPDDRIA FMLSDTGAKL VLAGEAHGSR VRGLTSGDVL 2530 2540 2550 2560 2570 2580 DLEQLDLTGE PAENPVTETT STELAYAIYT SGTTGKPKAV LVSHGSVDSF RAQLSGRYFG 2590 2600 2610 2620 2630 2640 SPDESAEAVL FLANYVFDFS VEQLALSVLG GHKLLVPPPS AADDPAFYEL ANREGLSYLS 2650 2660 2670 2680 2690 2700 GTPTQVERFD LARLSHLRCV LVAGEAFQPQ HFEKMRGEFA GPILNAYGTT ETTVYNTVHR 2710 2720 2730 2740 2750 2760 FEPGDAYRNT LGAPLGNTRL YVLGDGMKLL PTGAVGELYL AGDCVTEGYL HRPELTRERF 2770 2780 2790 2800 2810 2820 LPNPFAAESG RFPMIYRTGD VVRRGPDGEL QYLGRNDAQV KINGLRIEPG EVEAALAGCS 2830 2840 2850 2860 2870 2880 GVRQCAVVAG ADPQAPERKR LVGYYLPEPG AAVDEADLFA ALRAQLMPSM VPSLLVRLDR 2890 2900 2910 2920 2930 2940 PLPMTITGKL DVDALPSADF SPKRAAYAAP RDRVEARLCH LWSAQLPGGT VGIDDDFFRC 2950 2960 2970 2980 2990 3000 GGDSISALHL ASQVQREIER KVSVKYLFDH PTVRSFVDNV LSGLAESSGD DEPEQGRLTG 3010 3020 3030 3040 3050 3060 ECPMLPIQEW FFAKPLADRH RWNHNFAIRT PPLDPGELRT ALDRLVEHHD AFRLRFPESG 3070 3080 3090 3100 3110 3120 GEVYAEDAAP ITLHELDVRG LADADLRQRL VDWQRTFDLA NGPTACAAYL HGFDDGTARV 3130 3140 3150 3160 3170 3180 WFALHHLVVD TVSWHILAQD LEILYNGGDL GAKTGSYRQW AQAVRDYTPA EGEREFWAET 3190 3200 3210 3220 3230 3240 TRDMESAELL AQTEGTTRRR EEFALTAPDT RTLLAESPWA YDTEVNDLLL TATGFALRSI 3250 3260 3270 3280 3290 3300 TRQATNHLTV EGHGRELFEG APDVRDTVGW FTTMHPFAVE VDPGDLGRSV LATRANRRRV 3310 3320 3330 3340 3350 3360 PHHGIGYGAL FGGEAPLPAV SFNYLGRLGE GDGQPTEAWQ LDPALSGSHT VDGNRLANRS 3370 3380 3390 3400 3410 3420 SIDVTMSCTG GRLVAVVDSL LGEAATRLFA SELKVWLERL VSHTATVARN EPAREATTEL 3430 3440 3450 3460 3470 3480 FDPYILVNED AERTLFVLPP GEGGAESYLS NLARQLPDLR LVLFNNVHLH TPMGSFEELG 3490 3500 3510 3520 3530 3540 RYYVEHIRRL QPSGPYHLLG WSFGGVLSLE ISRQLARAGE RIDDLLLIDP YFGMRQASAN 3550 3560 3570 3580 3590 3600 IGLPGVEDIL DPINYHYRPD EADLARLAGR LGNLVLFKAG EPNDVVNGPH QPRLFEYYHG 3610 3620 3630 3640 TRFNHLDLLL PAAAIEVCDL AGETHHSWVR NEKLVRLMCE RISTSLGSD

References

[1]

"The cephamycin biosynthetic genes pcbAB, encoding a large multidomain peptide synthetase, and pcbC of Nocardia lactamdurans are clustered together in an organization different from the same genes in Acremonium chrysogenum and Penicillium chrysogenum." Coque J.J.R., Martin J.F., Calzada J.G., Liras P. Mol. Microbiol. 5:1125-1133(1991) [PubMed: 1956290] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: VAR LC 411.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X57310 Genomic DNA. Translation: CAA40561.1.
PIR	S18268.
3D structure databases
HSSP	HSSP built from PDB template 1DNY based on UniProtKB O30409.
ModBase	Search...
Enzyme and pathway databases
BRENDA	6.3.2.26. 261149.
Family and domain databases
InterPro	IPR010071. AA_adenyl_domain. IPR009081. Acyl_carrier_prot-like. IPR000873. AMP-dep_Synth/Lig. IPR001242. Condensatn. IPR006163. Phsphopanteth_bd. IPR006162. Ppantne_S. IPR001031. Thioesterase. [Graphical view]
Pfam	PF00501. AMP-binding. 3 hits. PF00668. Condensation. 3 hits. PF00550. PP-binding. 3 hits. PF00975. Thioesterase. 1 hit. [Graphical view]
TIGRFAMs	TIGR01733. AA-adenyl-dom. 3 hits.
PROSITE	PS50075. ACP_DOMAIN. 3 hits. PS00455. AMP_BINDING. 1 hit. PS00012. PHOSPHOPANTETHEINE. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ACVS_NOCLA

Accession

Primary (citable) accession number: P27743

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)