Reviewed, UniProtKB/Swiss-Prot P05189 (IPNS_CEPAC)

Names and origin

Protein names

Recommended name:
    Isopenicillin N synthetase
    EC=1.21.3.1
Alternative name(s):
    Isopenicillin N synthase
      Short name=IPNS

Gene names

Name:	PCBC
Synonyms:	IPS

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

General annotation (Comments)

Function	Removes, in the presence of oxygen, 4 hydrogen atoms from delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to form the azetidinone and thiazolidine rings of isopenicillin.
Catalytic activity	N-((5S)-5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine + O2 = isopenicillin N + 2 H2O.
Cofactor	Iron. Ascorbate.
Pathway	Antibiotic biosynthesis; penicillin G biosynthesis; penicillin G from L-alpha-aminoadipate and L-cysteine and L-valine: step 2/3.
Sequence similarities	Belongs to the iron/ascorbate-dependent oxidoreductase family.

Ontologies

Keywords
Biological process	Antibiotic biosynthesis
Ligand	Iron Metal-binding Vitamin C
Molecular function	Oxidoreductase
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	antibiotic biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW isopenicillin-N synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 338	338	Isopenicillin N synthetase		PRO_0000219499
Sites
	Metal binding	216	1	Iron
	Metal binding	218	1	Iron By similarity
	Metal binding	272	1	Iron
	Site	283	1	Involved in ACV-binding
Natural variations
	Natural variant	285	1	P → L in strain: N-2; inactive.
Experimental info
	Mutagenesis	216	1	H → L: Loss of activity. Ref.6 Ref.9 Ref.10
	Mutagenesis	218	1	D → L: Loss of activity. Ref.6 Ref.9 Ref.10 Ref.7
	Mutagenesis	234	1	Q → L: Loss of activity. Ref.6 Ref.9 Ref.10 Ref.8
	Mutagenesis	272	1	H → L: Loss of activity. Ref.6 Ref.9 Ref.10 Ref.5
	Mutagenesis	283	1	S → A: Loss of activity. Ref.6 Ref.9 Ref.10 Ref.11
	Sequence conflict	22	1	D → T AA sequence Ref.3
	Sequence conflict	177	1	S → F in AAA32674. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P05189-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: CFB0B6E27FC04EE9	FASTA	338	38,433
	10 20 30 40 50 60 MGSVPVPVAN VPRIDVSPLF GDDKEKKLEV ARAIDAASRD TGFFYAVNHG VDLPWLSRET 70 80 90 100 110 120 NKFHMSITDE EKWQLAIRAY NKEHESQIRA GYYLPIPGKK AVESFCYLNP SFSPDHPRIK 130 140 150 160 170 180 EPTPMHEVNV WPDEAKHPGF RAFAEKYYWD VFGLSSAVLR GYALALGRDE DFFTRHSRRD 190 200 210 220 230 240 TTLSSVVLIR YPYLDPYPEP AIKTADDGTK LSFEWHEDVS LITVLYQSDV QNLQVKTPQG 250 260 270 280 290 300 WQDIQADDTG FLINCGSYMA HITDDYYPAP IHRVKWVNEE RQSLPFFVNL GWEDTIQPWD 310 320 330 PATAKDGAKD AAKDKPAISY GEYLQGGLRG LINKNGQT

References

[1]	"Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium." Samson S.N., Belagaje R., Blankenship D.T., Chapman J.L., Perry D., Skatrud P.L., Vanfrank R.M., Abraham E.P., Baldwin J.E., Queener S.W., Ingolia T.D. Nature 318:191-194(1985) [PubMed: 3903520] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Characterization of a loss-of-function mutation in the isopenicillin N synthetase gene of Acremonium chrysogenum." Ramsden M., McQuade B.A., Saunders K., Turner M.K., Harford S. Gene 85:267-273(1989) [PubMed: 2620834] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: N-2.
[3]	"N-terminal amino acid sequence and some properties of isopenicillin-N synthetase from Cephalosporium acremonium." Baldwin J.E., Gagnon J., Ting H.H. FEBS Lett. 188:253-256(1985) [PubMed: 3839755] [Abstract] Cited for: PROTEIN SEQUENCE OF 3-52. Strain: ATCC 60777.
[4]	"Photoaffinity labelling of isopenicillin N synthetase." Baldwin J.E., Coates J.B., Moloney M.G., Pratt A.J., Willis A.C. Biochem. J. 266:561-567(1990) [PubMed: 2317203] [Abstract] Cited for: PROTEIN SEQUENCE OF 40-78 AND 237-264, PHOTOAFFINITY LABELLING.
[5]	"Histidine-272 of isopenicillin N synthase of Cephalosporium acremonium, which is possibly involved in iron binding, is essential for its catalytic activity." Tiow-Suan S., Tan D.S. FEMS Microbiol. Lett. 120:241-247(1994) [PubMed: 8076799] [Abstract] Cited for: MUTAGENESIS OF HIS-272.
[6]	"Functional analysis of conserved histidine residues in Cephalosporium acremonium isopenicillin N synthase by site-directed mutagenesis." Tan D.S., Sim T.S. J. Biol. Chem. 271:889-894(1996) [PubMed: 8557701] [Abstract] Cited for: MUTAGENESIS OF HISTIDINE RESIDUES.
[7]	"Functional analysis of a conserved aspartate D218 in Cephalosporium acremonium isopenicillin N synthase." Loke P., Sim J., Sim T.S. FEMS Microbiol. Lett. 157:137-140(1997) [PubMed: 9418249] [Abstract] Cited for: MUTAGENESIS OF ASP-218.
[8]	"Catalytic activity in Cephalosporium acremonium isopenicillin N synthase does not involve glutamine-234." Loke P., Sim T.S. Biochem. Biophys. Res. Commun. 248:559-561(1998) [PubMed: 9703965] [Abstract] Cited for: MUTAGENESIS OF GLN-234.
[9]	"Analysis of glutamines in catalysis in Cephalosporium acremonium isopenicillin N synthase by site-directed mutagenesis." Loke P., Sim T.S. Biochem. Biophys. Res. Commun. 252:472-475(1998) [PubMed: 9826554] [Abstract] Cited for: MUTAGENESIS OF GLUTAMINE RESIDUES.
[10]	"Involvement of a third histidine in the ferrous active site of isopenicillin N synthase of Cephalosporium acremonium repudiated by recombinant double histidine mutants." Tan D.S., Ang S.G., Sim T.S. Biochem. Mol. Biol. Int. 44:333-345(1998) [PubMed: 9530516] [Abstract] Cited for: MUTAGENESIS OF HISTIDINE RESIDUES.
[11]	"Mutational evidence for the role of serine-283 in Cephalosporium acremonium isopenicillin N synthase." Loke P., Sim T.S. FEMS Microbiol. Lett. 165:353-356(1998) [PubMed: 9841222] [Abstract] Cited for: MUTAGENESIS OF SER-283.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X03148 Genomic DNA. Translation: CAA26927.1. M33522 Genomic DNA. Translation: AAA32674.1.
PIR	S09312.
3D structure databases
HSSP	HSSP built from PDB template 1QJE based on UniProtKB P05326.
ModBase	Search...
Enzyme and pathway databases
BioCyc	MetaCyc:MON-13364.
BRENDA	1.21.3.1. 66776.
Family and domain databases
InterPro	IPR002057. Isopenicillin-N_synth_CS. IPR002283. Isopenicillin-N_synthase. IPR005123. Oxoglutarate/Fe-dep_Oase. [Graphical view]
Pfam	PF03171. 2OG-FeII_Oxy. 1 hit. [Graphical view]
PRINTS	PR00682. IPNSYNTHASE.
PROSITE	PS00185. IPNS_1. 1 hit. PS00186. IPNS_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

IPNS_CEPAC

Accession

Primary (citable) accession number: P05189
Secondary accession number(s): Q00047

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	June 16, 2009
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)