Reviewed, UniProtKB/Swiss-Prot P25464 (ACVS_CEPAC)

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

Cephalosporium acremonium (Acremonium chrysogenum)

Taxonomic identifier

5044 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Sordariomycetes › Hypocreomycetidae › Hypocreales › mitosporic Hypocreales › Acremonium

Protein attributes

Sequence length	3712 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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 Potential.
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	Direct protein sequencing 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 – 3712	3712	N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase		PRO_0000193058
Regions
	Domain	795 – 864	70	Acyl carrier 1
	Domain	1880 – 1953	74	Acyl carrier 2
	Domain	2960 – 3027	68	Acyl carrier 3
	Region	234 – 1062	829	Domain 1 (adipate-activating)
	Region	1335 – 2162	828	Domain 2 (cysteine-activating)
	Region	2409 – 3387	979	Domain 3 (valine-activating)
Sites
	Active site	3568	1	For thioesterase activity By similarity
Amino acid modifications
	Modified residue	827	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	1916	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	2990	1	O-(pantetheine 4'-phosphoryl)serine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P25464-1 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 4EE3C1EB5EBEF9B7	FASTA	3,712	414,775
	10 20 30 40 50 60 MALEQWKTTV QSVSERCDLS GLSQHPTDYQ LASTGVKGAG GSSIEERSAI VSDELFSSLR 70 80 90 100 110 120 DVCSQRQLDP RSLMLFSVHQ MLKRFGNGSH TVVASLVTSS EGCPSTSAWR AIPSVIHHIE 130 140 150 160 170 180 GGDNNNTVAS AVEQAANLLN SEGSGQDLLI PIGLTELVKS ELIDLLVIFD DETNNIRLPQ 190 200 210 220 230 240 DFPLILRIHQ RQDHWQLSVR YPSPLFDTMV IDSFLSALHN LLSAVTKPSQ LVRDIELLPE 250 260 270 280 290 300 YQVAQLEKWN NTDGDYPTEK RLHHLFEEAA VRRPQHVALI CGDKRITYEE LNAMANRLAH 310 320 330 340 350 360 HLVSSGIQTE QLVGLFLDKT ELMIATILGI WKSGAAHVPI DPGYPDERVK FVLNDTKAQV 370 380 390 400 410 420 VIASQRHVDR LRAEAVGGQH LRIIGLESLF DNLAQQTQHS PETSGNLTHL PLNSKQLAYV 430 440 450 460 470 480 TYTSGTTGFP KGIYKEHTSV VNSITDLSAR YGVAGEDDEV ILVFSAYVFE PFVRQMLMAL 490 500 510 520 530 540 TTGNSLAIIS DEDKFDPDTL IPFIQKHKVT YIHATSSVLQ EYDFGSCPSL KRMILVGENL 550 560 570 580 590 600 TEPRYEALRQ RFKSRILNEY GFTESAFVTA LNIFEPTSQR KDMSLGRPVR NVKCYILDAN 610 620 630 640 650 660 LKRVPIGVTG ELHIGGLGIS RGYMNREELT RQKFLPNPYQ TDKERQRGVN STMYKTGDLA 670 680 690 700 710 720 RWLPSGEVEY LGRADFQIKL RGIRIEPGEI ESTLAMYPGI RASIVVSKKL LSQGQETIQD 730 740 750 760 770 780 HLVGYYVCDE GHIPEGDLLS FLEKKLPRYM VPTRLVQLAQ IPTNINGKAD LRALPAVEVA 790 800 810 820 830 840 VAPTHKQDGE RGNQLESDLA AIWGNILSVP AQDIGSESNF FRLGGHSIAC IQLIARVRQQ 850 860 870 880 890 900 LGQGITLEEV FQTKTLRAMA ALLSEKYTKA SNGTNGVTNG TAHVNGHAAN GHVSDSYVAS 910 920 930 940 950 960 SLQQGFVYHS LKNELSEAYT MQSMIHYGVP LKRDIYQAAW QRVQGEHPAL RLRFTWEAEV 970 980 990 1000 1010 1020 MQIVDPKSEL DWRVVDWTDV SSREKQLVAL EQLQTEDLAK VYHLDKGPLM RLYLILLPDS 1030 1040 1050 1060 1070 1080 KYSCLFSCHH AILDGWSLPL LFNNVHQAYL DLVEGTASPV EQDATYLLGQ QYLQSHRDDH 1090 1100 1110 1120 1130 1140 LDFWAEQIGR IEERCDMNAL LNEASRYKVP LADYDQVREQ RQQTISLPWN NSMDAGVREE 1150 1160 1170 1180 1190 1200 LSSRGITLHS ILQTVWHLVL HSYGGGTHTI TGTTISGRHL PVPGIERSVG LFINTLPMIF 1210 1220 1230 1240 1250 1260 DHTVCQDMTA LEAIEHVQGQ VNAMNSRGNV ELGRMSKNDL KHGLFDTLFV LENYPNLDTE 1270 1280 1290 1300 1310 1320 QREKHEEKLK FTIKGGTEKL SYPLAVIAQE DGDSGCSFTL CYAGELFTDE SIQALLDTVR 1330 1340 1350 1360 1370 1380 DTLSDILGNI HAPIRNMEYL SSNQTAQLDK WNATAFEYPN TTLHAMFESE AQQKPDKVAV 1390 1400 1410 1420 1430 1440 VYEDIRLTYR ELNSRANALA FYLLSQAAIQ PNKLVGLIMD KSEHMITSIL AVWKTGGAYV 1450 1460 1470 1480 1490 1500 PIDPRYPDQR IQYILEDTAA LAVITDSPHI DRLRSITNNR LPVIQSDFAL QLPPSPVHPV 1510 1520 1530 1540 1550 1560 SNCKPSDLAY IMYTSGTTGN PKGVMVEHHG VVNLCVSLCR LFGLRNTDDE VILSFSNYVF 1570 1580 1590 1600 1610 1620 DHFVEQMTDA LLNGQTLVVL NDEMRGDKER LYRYIETNRV TYLSGTPSVI SMYEFDRFRD 1630 1640 1650 1660 1670 1680 HLRRVDCVGE AFSEPVFDKI RETFPGLIIN GYGPTEVSIT THKRPYPFPE RRTDKSIGCQ 1690 1700 1710 1720 1730 1740 LDNSTSYVLN DDMKRVPIGA VGELYLGGDG VARGYHNRPD LTADRFPANP FQTEQERLEG 1750 1760 1770 1780 1790 1800 RNARLYKTGD LVRWIHNANG DGEIEYLGRN DFQVKIRGQR IELGEIEAVL SSYPGIKQSV 1810 1820 1830 1840 1850 1860 VLAKDRKNDG QKYLVGYFVS SAGSLSAQAI RRFMLTSLPD YMVPAQLVPI AKFPVTVSGK 1870 1880 1890 1900 1910 1920 LDAKALPVPD DTVEDDIVPP RTEVERILAG IWSELLEIPV DRISIYSDFF SLGGDSLKST 1930 1940 1950 1960 1970 1980 KLSFAATRAL GVAVSVRNLF SHPTIEALSQ WIIRGSNEVK DVAVVKGGAS LDIPLSPAQE 1990 2000 2010 2020 2030 2040 RLMFIHEFGH SGEDTGAYNV PLQLQLHHDV CLESLEKALR DVVSRHEALR TLITRTQKSS 2050 2060 2070 2080 2090 2100 VHCQKILDAE EAQKLFSVDV LRLTSETEMQ GRMAESTAHA FKLDEELPIH VRLYQVVRDG 2110 2120 2130 2140 2150 2160 RTLSFASIVC HHLAFDAWSW DVFQRDLDAF YAVHTKHKAA ANLPTLRVQY KEYAIEHRRA 2170 2180 2190 2200 2210 2220 LRAEQHRVLA DYWLRKLSDM EASYLVPDRP RPAQFDYTGN DLQFSTTPET TAQLKELAKR 2230 2240 2250 2260 2270 2280 EGSSLYTVVA AAYFLLLYVY TNQRDITIGI PVAHRNHPDF ESVVGFFVNL LPLRVNVSQS 2290 2300 2310 2320 2330 2340 DIHGLIQAVQ KELVDAQIHQ DLPFQEITKL LHVQHDPSRH PLLQAVFNWE NVPANVHEEQ 2350 2360 2370 2380 2390 2400 LLQEYKPPSP LPSAAKFDLN VTVKESVNSL NVNFNYPTSL FEEETVQGFM ETFHLLLRQL 2410 2420 2430 2440 2450 2460 AHNKASTSLS KLSVEDGVLN PEPTNLQPSS RDSGNSLHGL FEDIVASTPD RIAIADGTRS 2470 2480 2490 2500 2510 2520 LSYSELNERA NQLVHLIISS ASIVADDRIA LLLDKSIDMV IALLAVWKAG AAYVPLDPTY 2530 2540 2550 2560 2570 2580 PSQRTELILE ESSARTLITT RKHTPRGGTV ANVPSVVLDS PETLACLNQQ SKENPTTSTQ 2590 2600 2610 2620 2630 2640 KPSDLAYVIF TSGTTGKPKG VLVEHQSVVQ LRNSLIERYF GETNGSHAVL FLSNYVFDFS 2650 2660 2670 2680 2690 2700 LEQLCLSVLG GNKLIIPPEE GLTHEAFYDI GRREKLSYLS GTPSVLQQIE LSRLPHLHMV 2710 2720 2730 2740 2750 2760 TAAGEEFHAS QFEKMRSQFA GQINNAYGIT ETTVYNIITT FKGDAPFTKA LCHGIPGSHV 2770 2780 2790 2800 2810 2820 YVLNDRLQRV PFNAVGELYL GGDCLARGYL NQDALTNERF IPNPFYEPKQ ASDSRPQRLY 2830 2840 2850 2860 2870 2880 KTGDLVRFRG PHHLEYLGRK DQQVKLRGFR IELSEVRDAV LAISAVKEAA VIPKYDEDGS 2890 2900 2910 2920 2930 2940 DSRRVSAIVC YYTLNAGTVC EASSIRDHLH ANLPPYMVPS QIHQLEGSLP VTVNGKLDLN 2950 2960 2970 2980 2990 3000 RLSTTQVSQP ELYTAPRNST EETLCQLWAS LLGVDHCGID DDLFARGGDS ISSLRLVGDI 3010 3020 3030 3040 3050 3060 YRALGRKVTV KDIYLHRSVR ALSENVLTDQ KDKGTLPASP PLQRAEQGQV EGDAPLLPIQ 3070 3080 3090 3100 3110 3120 DWFLSKPLDN PAYWNHCFTI RTGALSVEGL RGALKLLQER HDVLRLRLQR RDEGRHVQTF 3130 3140 3150 3160 3170 3180 ARDCAQPRLT VLDRRSFEDA EDVQEALCEI QSHFDLENGP LYTVAYIHGY EDGSARVWFA 3190 3200 3210 3220 3230 3240 CHHVMVDTVS WNIILQDLQA LYHGDSLGPK SSSVQQWSLA VSDYKMPLSE RAHWNVLRKT 3250 3260 3270 3280 3290 3300 VAQSFETLPI CMGGVLQCQE KFSRETTTAL LSKACPALDS GMHEILLMAV GSALQKAAGD 3310 3320 3330 3340 3350 3360 VPQVVTIEGH GREDTIDATL DVSRTVGWFT SMYPFEIPKV TDPAQGVVDV KEAMRRVPNR 3370 3380 3390 3400 3410 3420 GVGYGPAYGY GGSCLPAVSF NYLGRLDQAS SGAQRDWTLV MDEDEYPVGL CTSAEDSGRS 3430 3440 3450 3460 3470 3480 SSMVDFTFSI SGGQLVMDMS SSWGHGARNE FVRTVRNTLD DLIKTTSSRD FSAPLPPSDQ 3490 3500 3510 3520 3530 3540 ESSFTPYFVF EEGERHGAPL FLLPPGEGGA ESYFHNIVKG LPNRNLVVFN NHYREEKTLR 3550 3560 3570 3580 3590 3600 TIEALAEYYL SHIRSIQPEG PYHILGWSFG GILGLEAAKR LTGEGHKIAT LALIDPYFDI 3610 3620 3630 3640 3650 3660 PSASKAIGQP DDACVLDPIY HVYHPSPESF RTVSSLTNHI ALFKATETND QHGNATQQAL 3670 3680 3690 3700 3710 YEWFATCPLN NLDKFLAADT IKVVPLEGTH FTWVHHPEQV RSMCTMLDEW LG

References

[1]

"Characterization of the Cephalosporium acremonium pcbAB gene encoding alpha-aminoadipyl-cysteinyl-valine synthetase, a large multidomain peptide synthetase: linkage to the pcbC gene as a cluster of early cephalosporin biosynthetic genes and evidence of multiple functional domains." Gutierrez S., Diez B., Montenegro E., Martin J.F. J. Bacteriol. 173:2354-2365(1991) [PubMed: 1706706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.

[2]

"Gene disruption of the pcbAB gene encoding ACV synthetase in Cephalosporium acremonium." Hoskins J.A., O'Callaghan N., Queener S.W., Cantwell C.A., Wood J.S., Chen V.J., Skatrud P.L. Curr. Genet. 18:523-530(1990) [PubMed: 2076552] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE, PARTIAL PROTEIN SEQUENCE. Strain: ATCC 11550 / CBS 779.69 / DSM 880 / IMI 49137.

Cross-references

Sequence databases
PIR	YGCEVC. A38531.
3D structure databases
HSSP	HSSP built from PDB template 1AMU based on UniProtKB P14687.
ModBase	Search...
Enzyme and pathway databases
BRENDA	6.3.2.26. 66776.
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. 3 hits. PS00012. PHOSPHOPANTETHEINE. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ACVS_CEPAC

Accession

Primary (citable) accession number: P25464

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 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

FPAP (Fungal Proteome Annotation Project)