PDBsum entry 1w3v

Synthase

PDB id

1w3v

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Contents

			Protein chain

					329 a.a. *

			Ligands

					MDZ

			Metals

					FE2

			Waters ×284

* Residue conservation analysis

PDB id:

1w3v

Links

Name:

Synthase

Title:

Isopenicillin n synthase d-(l-a-aminoadipoyl)-(3r)-methyl-l-cysteine d-a-hydroxyisovaleryl ester complex (anaerobic)

Structure:

Isopenicillin n synthetase. Chain: a. Synonym: ipns, isopenicillin n synthase. Engineered: yes

Source:

Emericella nidulans (strain fgsc a4 / atcc 38163 / cbs 112.46 / nrrl 194 / m139). Aspergillus nidulans. Organism_taxid: 227321. Gene: pcb c. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details:

Resolution:

1.40Å

R-factor:

0.162

R-free:

0.175

Authors:

A.Daruzzaman,I.J.Clifton,P.J.Rutledge

Key ref:

A.Daruzzaman et al. (2006). Unexpected oxidation of a depsipeptide substrate analogue in crystalline isopenicillin N synthase. Chembiochem, 7, 351-358. PubMed id: 16444759 DOI: 10.1002/cbic.200500282

Date:

20-Jul-04

Release date:

07-Dec-05

PROCHECK

	Headers

	References

Protein chain

P05326 (IPNS_EMENI) - Isopenicillin N synthase from Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)

Seq: Struc:					331 a.a. 329 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.1.21.3.1 - isopenicillin-N synthase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Penicillin N and Deacetoxycephalosporin C Biosynthesis

Reaction:

N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine + O2 = isopenicillin N + 2 H2O

N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine	+	O2	=	isopenicillin N	+	2 × H2O Bound ligand (Het Group name = MDZ) matches with 48.48% similarity

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1002/cbic.200500282	Chembiochem 7:351-358 (2006)
PubMed id: 16444759

Unexpected oxidation of a depsipeptide substrate analogue in crystalline isopenicillin N synthase.
A.Daruzzaman, I.J.Clifton, R.M.Adlington, J.E.Baldwin, P.J.Rutledge.

ABSTRACT

Isopenicillin N synthase (IPNS) is a non-heme iron(ii)-dependent oxidase that is central to penicillin biosynthesis. Herein, we report mechanistic studies of the IPNS reaction in the crystalline state, using the substrate analogue delta-(L-alpha-aminoadipoyl)-(3R)-methyl-L-cysteine D-alpha-hydroxyisovaleryl ester (AmCOV) to probe the early stages of the catalytic cycle. The X-ray crystal structure of the anaerobic IPNS:Fe(II):AmCOV complex was solved to 1.40 A resolution, and it reveals several subtle differences in the active site relative to the complex of the enzyme with its natural substrate. The crystalline IPNS:Fe(II):AmCOV complex was then exposed to oxygen gas at high pressure; this brought about reaction to give what appears to be a hydroxymethyl/ene-thiol product. A mechanism for this reaction is proposed. These results offer further insight into the delicate interplay of steric and electronic effects in the IPNS active site and the mechanistic intricacies of this remarkable enzyme.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20237680

V.J.Dungan, Y.Ortin, H.Mueller-Bunz, and P.J.Rutledge (2010).
Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site.

Org Biomol Chem, 8, 1666-1673.

19598184

W.Ge, I.J.Clifton, A.R.Howard-Jones, J.E.Stok, R.M.Adlington, J.E.Baldwin, and P.J.Rutledge (2009).
Structural studies on the reaction of isopenicillin N synthase with a sterically demanding depsipeptide substrate analogue.

Chembiochem, 10, 2025-2031.

PDB code:

2vcm

19020684

P.C.Bruijnincx, G.van Koten, and R.J.Klein Gebbink (2008).
Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies.

Chem Soc Rev, 37, 2716-2744.

17907118

A.C.Stewart, I.J.Clifton, R.M.Adlington, J.E.Baldwin, and P.J.Rutledge (2007).
A cyclobutanone analogue mimics penicillin in binding to isopenicillin N synthase.

Chembiochem, 8, 2003-2007.

PDB code:

2jb4

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.