P05326 (IPNS_EMENI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isopenicillin N synthase
Short name=IPNS
EC=1.21.3.1

Gene names

Name:	ipnA
Synonyms:	ips
ORF Names:	AN2622

Organism

Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) [Reference proteome]

Taxonomic identifier

227321 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Pezizomycotina › leotiomyceta › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Trichocomaceae › Emericella › Emericella nidulans › mitosporic Emericella nidulans

Protein attributes

Sequence length	331 AA.
Sequence status	Complete.
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. Contains 1 Fe2OG dioxygenase domain.

Ontologies

Keywords
Biological process	Antibiotic biosynthesis
Ligand	Iron Metal-binding Vitamin C
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antibiotic biosynthetic process 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: InterPro isopenicillin-N synthase activity Inferred from electronic annotation. Source: EC oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors 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 – 331

331

Isopenicillin N synthase

PRO_0000219498

Regions

Domain

176 – 288

113

Fe2OG dioxygenase

Sites

Metal binding

214

1

Iron

Metal binding

216

1

Iron

Metal binding

270

1

Iron

Secondary structure

1

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331

Helix Strand Turn

Details...

Beta strand

11 – 13

3

Helix

15 – 18

4

Helix

22 – 37

16

Beta strand

40 – 46

7

Helix

51 – 64

14

Helix

67 – 73

7

Turn

76 – 78

3

Beta strand

86 – 91

6

Turn

95 – 97

3

Beta strand

101 – 105

5

Helix

115 – 118

4

Turn

132 – 134

3

Helix

138 – 163

26

Turn

168 – 171

4

Helix

172 – 174

3

Turn

177 – 179

3

Beta strand

183 – 189

7

Helix

197 – 199

3

Beta strand

208 – 214

7

Beta strand

217 – 225

9

Beta strand

231 – 235

5

Beta strand

238 – 241

4

Beta strand

248 – 253

6

Helix

255 – 260

6

Turn

261 – 263

3

Beta strand

270 – 273

4

Beta strand

279 – 286

8

Beta strand

301 – 303

3

Helix

313 – 328

16

Sequences

	Sequence		Length	Mass (Da)
	P05326 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 5BA1A726E9EEFA25	FASTA	331	37,522
	10 20 30 40 50 60 MGSVSKANVP KIDVSPLFGD DQAAKMRVAQ QIDAASRDTG FFYAVNHGIN VQRLSQKTKE 70 80 90 100 110 120 FHMSITPEEK WDLAIRAYNK EHQDQVRAGY YLSIPGKKAV ESFCYLNPNF TPDHPRIQAK 130 140 150 160 170 180 TPTHEVNVWP DETKHPGFQD FAEQYYWDVF GLSSALLKGY ALALGKEENF FARHFKPDDT 190 200 210 220 230 240 LASVVLIRYP YLDPYPEAAI KTAADGTKLS FEWHEDVSLI TVLYQSNVQN LQVETAAGYQ 250 260 270 280 290 300 DIEADDTGYL INCGSYMAHL TNNYYKAPIH RVKWVNAERQ SLPFFVNLGY DSVIDPFDPR 310 320 330 EPNGKSDREP LSYGDYLQNG LVSLINKNGQ T

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans." Ramon D., Carramolino L., Patino C., Sanchez F., Penalva M.A. Gene 57:171-181(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning and expression in Escherichia coli of isopenicillin N synthetase genes from Streptomyces lipmanii and Aspergillus nidulans." Weigel B.J., Burgett S.G., Chen V.J., Skatrud P.L., Frolik C.A., Queener S.W., Ingolia T.D. J. Bacteriol. 170:3817-3826(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae." Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S., Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V., Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S., Braus G.H. , Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H., Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K., Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R., Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C., Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L., Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W. Nature 438:1105-1115(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139.
[4]	"The 2008 update of the Aspergillus nidulans genome annotation: a community effort." Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J., Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H., Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M., Estrada C.G. , Geysens S., Goldman G., de Groot P.W., Hansen K., Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G., Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L., Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M., van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P., Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J., Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A., Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X., Robson G., Seiboth B., van Solingen P., Specht T., Sun J., Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H., van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y., Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J., Oliver S.G., Turner G. Fungal Genet. Biol. 46:S2-13(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139.
[5]	"Crystallization and preliminary X-ray diffraction studies on recombinant isopenicillin N synthase from Aspergillus nidulans." Roach P.L., Schofield C.J., Baldwin J.E., Clifton I.J., Hajdu J. Protein Sci. 4:1007-1009(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CRYSTALLIZATION.
[6]	"Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes." Roach P.L., Clifton I.J., Fueloep V., Harlos K., Barton G.J., Hajdu J., Andersson I., Schofield C.J., Baldwin J.E. Nature 375:700-704(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[7]	"Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation." Roach P.L., Clifton I.J., Hensgens C.M., Shibata N., Schofield C.J., Hajdu J., Baldwin J.E. Nature 387:827-830(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS).
[8]	"The reaction cycle of isopenicillin N synthase observed by X-ray diffraction." Burzlaff N.I., Rutledge P.J., Clifton I.J., Hensgens C.M.H., Pickford M., Adlington R.M., Roach P.L., Baldwin J.E. Nature 401:721-724(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS).
[9]	"Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction." Ogle J.M., Clifton I.J., Rutledge P.J., Elkins J.M., Burzlaff N.I., Adlington R.M., Roach P.L., Baldwin J.E. Chem. Biol. 8:1231-1237(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M18111 Genomic DNA. Translation: AAA33311.1.
M21882 Genomic DNA. Translation: AAA33310.1.
AACD01000045 Genomic DNA. Translation: EAA62969.1.
BN001306 Genomic DNA. Translation: CBF84347.1.

PIR

A27355.

RefSeq

XP_660226.1. XM_655134.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BK0	X-ray	1.30	A	1-331	[»]
1BLZ	X-ray	1.45	A	1-331	[»]
1HB1	X-ray	1.55	A	1-331	[»]
1HB2	X-ray	1.30	A	1-331	[»]
1HB3	X-ray	1.40	A	1-331	[»]
1HB4	X-ray	1.50	A	1-331	[»]
1IPS	X-ray	2.50	A/B	1-331	[»]
1OBN	X-ray	1.30	A	1-331	[»]
1OC1	X-ray	2.20	A	1-331	[»]
1ODM	X-ray	1.15	A	1-331	[»]
1ODN	X-ray	1.60	A	1-331	[»]
1QIQ	X-ray	1.50	A	1-331	[»]
1QJE	X-ray	1.35	A	1-331	[»]
1QJF	X-ray	1.40	A	1-331	[»]
1UZW	X-ray	1.30	A	1-331	[»]
1W03	X-ray	2.10	A	1-331	[»]
1W04	X-ray	1.28	A	1-331	[»]
1W05	X-ray	2.46	A	1-331	[»]
1W06	X-ray	1.65	A	1-331	[»]
1W3V	X-ray	1.40	A	1-331	[»]
1W3X	X-ray	1.46	A	1-331	[»]
2BJS	X-ray	1.30	A	1-325	[»]
2BU9	X-ray	1.30	A	1-331	[»]
2IVI	X-ray	1.30	B	1-331	[»]
2IVJ	X-ray	1.46	A	1-331	[»]
2JB4	X-ray	1.30	A	1-331	[»]
2VAU	X-ray	1.80	A	1-331	[»]
2VBB	X-ray	1.40	A	1-331	[»]
2VBD	X-ray	2.00	A	1-331	[»]
2VBP	X-ray	1.50	A	1-331	[»]
2VCM	X-ray	1.65	A	1-331	[»]
2VE1	X-ray	2.20	A	1-331	[»]
2WO7	X-ray	2.50	A	1-331	[»]
2Y60	X-ray	1.40	A	1-331	[»]
2Y6F	X-ray	1.79	A	1-331	[»]
2Y86	X-ray	1.82	A	1-331	[»]
3ZKU	X-ray	1.40	A	1-331	[»]

ProteinModelPortal

P05326.

SMR

P05326. Positions 3-331.

ModBase

Search...

Protein-protein interaction databases

STRING

162425.CADANIAP00010504.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

CADANIAT00010504; CADANIAP00010504; CADANIAG00010504.

GeneID

2874542.

KEGG

ani:AN2622.2.

Phylogenomic databases

eggNOG

COG3491.

HOGENOM

HOG000089437.

OrthoDB

EOG4CC790.

Enzyme and pathway databases

UniPathway

UPA00149; UER00240.

Family and domain databases

InterPro

IPR026992. DIOX_N.
IPR002057. Isopenicillin-N_synth_CS.
IPR002283. Isopenicillin-N_synthase.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]

Pfam

PF03171. 2OG-FeII_Oxy. 1 hit.
PF14226. DIOX_N. 1 hit.
[Graphical view]

PRINTS

PR00682. IPNSYNTHASE.

PROSITE

PS51471. FE2OG_OXY. 1 hit.
PS00185. IPNS_1. 1 hit.
PS00186. IPNS_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P05326.

Entry information

Entry name

IPNS_EMENI

Accession

Primary (citable) accession number: P05326
Secondary accession number(s): C8VHS7, Q5BA08

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	November 1, 1988
Last modified:	April 3, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program