Overview for MACiE Entry M0137
EC Number: 18.104.22.168 (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:
- 22.214.171.1240 - B-lactam Antibiotic, Isopenicillin N Synthase; Chain
Display structure information
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 . The mechanism shown comes from steady-state kinetic data, quantum-chemical calculations and structural studies .
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Stepwise Description of the Reaction
|Step 1||2-oxoglutarate initiates an electrophilic addition to dioxygen, which coordinates to the Fe(II) cofactor.|
|Step 2||Carbon dioxide is eliminated from the intermediate to form a planar peroxo intermediate. Carbon dioxide is still coordinated to the Fe(II) cofactor.|
|Step 3||Fe(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 4||Penicillin 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 5||A colligation occurs between the alkyl radical and the sulfur of the five membered ring in the penicillin.|
|Step 6||The C-S bond of the original five-mebered ring homolyses, producing the six-membered ring.|
|Step 7||The 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
- K. Valegard et al. (2004), Nat. Struct. Mol. Biol., 11, 95-101. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme.
- 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.
- H. J. Lee et al. (2001), J. Mol. Biol., 308, 937-948. Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS).
Homologue information for M0137 (1unb)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Links to this entry in other databases