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PDBsum entry 1w3v

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protein ligands metals links
Synthase PDB id
1w3v
Jmol
Contents
Protein chain
329 a.a. *
Ligands
MDZ
Metals
FE2
Waters ×284
* Residue conservation analysis
PDB id:
1w3v
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. Organism_taxid: 162425. Gene: pcb c. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details:
Resolution:
1.4Å     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
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05326  (IPNS_EMENI) -  Isopenicillin N synthase
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
+ O(2)
=
isopenicillin N
Bound ligand (Het Group name = MDZ)
matches with 48.00% similarity
+ 2 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cellular_component   1 term 
  Biological process     biosynthetic process   5 terms 
  Biochemical function     oxidoreductase activity     7 terms  

 

 
    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.