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Overview for MACiE Entry M0137

Version history

General Information

EC Number: 1.14.20.1 (A member of the Oxidoreductases, Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2, With 2-oxoglutarate as one donor, and the other dehydrogenated)

Enzyme Name: deacetoxycephalosporin-C synthase

Biological Species: Streptomyces clavuligerus (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P18548 - Deacetoxycephalosporin C synthase

Representative PDB Code: 1unb - DEACETOXYCEPHALOSPORIN C SYNTHASE COMPLEXED WITH2-OXOGLUTARATE AND AMPICILLIN (Resolution = 1.50 Å).

Catalytic CATH Codes:

  • This enzyme has no catalytic CATH domains assigned

"Other" CATH Codes:

  • 2.60.120.330 - B-lactam Antibiotic, Isopenicillin N Synthase; Chain

Display structure information

Overall Reaction:

Image of oxygen

Image of penicilin N

Image of 2-oxoglutarate

right arrow

Image of carbon dioxide

Image of deacetoxycephalosporin C

Image of succinate

Image of water

oxygen
C00007
CHEBI:15379
penicilin N
C06564
CHEBI:58408
2-oxoglutarate
C00026
CHEBI:16810
carbon dioxide
C00011
CHEBI:16526
deacetoxycephalosporin C
C06565
CHEBI:58415
succinate
C00042
CHEBI:30031
water
C00001
CHEBI:15377

Overall Comment: The absence of obvious residues to catalyse general acid-base processes in the active site of this enzyme suggests that the covalent bond cleavage/formation reactions are all mediated by iron centred intermediates [2]. The mechanism shown comes from steady-state kinetic data, quantum-chemical calculations and structural studies [1].


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Stepwise Description of the Reaction

Step 12-oxoglutarate initiates an electrophilic addition to dioxygen, which coordinates to the Fe(II) cofactor.
Step 2Carbon dioxide is eliminated from the intermediate to form a planar peroxo intermediate. Carbon dioxide is still coordinated to the Fe(II) cofactor.
Step 3Fe(II) initiates an elimination reaction by donating two electrons to the bound peroxo moiety, cleaving the peroxo bond and producing the succinate product and iron as a ferryl species.
Step 4Penicillin binds, displacing the succinate and carbon dioxide as iron ligands. The oxo group deprotonates the CH3 of the penicillin, generating a alkyl radical and resulting in the donation of a single electron to Fe(IV).
Step 5A colligation occurs between the alkyl radical and the sulfur of the five membered ring in the penicillin.
Step 6The C-S bond of the original five-mebered ring homolyses, producing the six-membered ring.
Step 7The carbon radical in the ring donates a single electron to the Fe(III) cofactor, which causes the bound hydroxide to deprotonate the C3 of the thiazolidine ring generating the final deacetoxycephalosporin C product.

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Catalytic Residues Involved

There are no catalytic residues associated with this reaction mechanism


Metal Cofactors for M0137

Type Het group Number Chain
iron FE2 1310 A Overview

References

  1. K. Valegard et al. (2004), Nat. Struct. Mol. Biol., 11, 95-101. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme.
    Medline: 14718929
  2. I. J. Clifton et al. (2006), J. Inorg. Biochem., 100, 644-669. Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins.
    Medline: 16513174
  3. H. J. Lee et al. (2001), J. Mol. Biol., 308, 937-948. Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS).
    Medline: 11352583

Homologue information for M0137 (1unb)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

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iron ion binding (molecular function)
biosynthetic process (biological process)
oxidoreductase activity (molecular function)
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 (molecular function)
antibiotic biosynthetic process (biological process)
L-ascorbic acid binding (molecular function)
deacetoxycephalosporin-C synthase activity (molecular function)
oxidation-reduction process (biological process)
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