PDBsum entry 1w05

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Oxidoreductase PDB id
Protein chain
329 a.a. *
Waters ×317
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Isopenicillin n synthase aminoadipoyl-cysteinyl-alanine-fe complex
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:
2.46Å     R-factor:   0.162     R-free:   0.214
Authors: A.J.Long,I.J.Clifton,P.J.Rutledge
Key ref:
A.J.Long et al. (2005). Structural studies on the reaction of isopenicillin N synthase with the truncated substrate analogues delta-(L-alpha-aminoadipoyl)-L-cysteinyl-glycine and delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alanine. Biochemistry, 44, 6619-6628. PubMed id: 15850395 DOI: 10.1021/bi047478q
01-Jun-04     Release date:   04-May-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05326  (IPNS_EMENI) -  Isopenicillin N synthase
331 a.a.
329 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Isopenicillin-N synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Penicillin N and Deacetoxycephalosporin C Biosynthesis
      Reaction: N-((5S)-5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine + O2 = isopenicillin N + 2 H2O
+ O(2)
isopenicillin N
Bound ligand (Het Group name = W05)
matches with 91.67% 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: 10.1021/bi047478q Biochemistry 44:6619-6628 (2005)
PubMed id: 15850395  
Structural studies on the reaction of isopenicillin N synthase with the truncated substrate analogues delta-(L-alpha-aminoadipoyl)-L-cysteinyl-glycine and delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alanine.
A.J.Long, I.J.Clifton, P.L.Roach, J.E.Baldwin, P.J.Rutledge, C.J.Schofield.
Isopenicillin N synthase (IPNS), a non-heme iron(II)-dependent oxidase, catalyzes conversion of the tripeptide delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to bicyclic isopenicillin N (IPN), concomitant with the reduction of dioxygen to two molecules of water. Incubation of the "truncated"substrate analogues delta-(l-alpha-aminoadipoyl)-l-cysteinyl-glycine (ACG) and delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alanine (ACA) with IPNS has previously been shown to afford acyclic products, in which the substrate cysteinyl residue has undergone a two-electron oxidation. We report X-ray crystal structures for the anaerobic IPNS/Fe(II)/ACG and IPNS/Fe(II)/ACA complexes, both in the absence and presence of the dioxygen analogue nitric oxide. The overall protein structures are very similar to those of the corresponding IPNS/Fe(II)/ACV complexes; however, significant differences are apparent in the vicinity of the active site iron. The structure of the IPNS/Fe(II)/ACG complex reveals that the C-terminal carboxylate of this substrate is oriented toward the active site iron atom, apparently hydrogen-bonded to an additional water ligand at the metal; this is a different binding mode to that observed in the IPNS/Fe(II)/ACV complex. ACA binds to the metal in a manner that is intermediate between those observed for ACV and ACG. The addition of NO to these complexes initiates conformational changes such that both the IPNS/Fe(II)/ACG/NO and IPNS/Fe(II)/ACA/NO structures closely resemble the IPNS/Fe(II)/ACV/NO complex. These results further demonstrate the feasibility of metal-centered rearrangements in catalysis by non-heme iron enzymes and provide insight into the delicate balance between hydrophilic-hydrophobic interactions and steric effects in the IPNS active site.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20218986 A.Benjdia, S.Subramanian, J.Leprince, H.Vaudry, M.K.Johnson, and O.Berteau (2010).
Anaerobic sulfatase-maturating enzyme--a mechanistic link with glycyl radical-activating enzymes?
  FEBS J, 277, 1906-1920.  
20078029 C.D.Brown-Marshall, A.R.Diebold, and E.I.Solomon (2010).
Reaction coordinate of isopenicillin N synthase: oxidase versus oxygenase activity.
  Biochemistry, 49, 1176-1182.  
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
16444759 A.Daruzzaman, I.J.Clifton, R.M.Adlington, J.E.Baldwin, and P.J.Rutledge (2006).
Unexpected oxidation of a depsipeptide substrate analogue in crystalline isopenicillin N synthase.
  Chembiochem, 7, 351-358.
PDB codes: 1w3v 1w3x
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