1ODN

ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN-EXPOSED PRODUCT FROM ANAEROBIC AC-VINYLGLYCINE FE COMPLEX)

Summary for 1ODN

• Entry DOI: 10.2210/pdb1odn/pdb
• Related: 1BK0 1BLZ 1HB1 1HB2 1HB3 1HB4 1IPS 1OBN 1OC1 1ODM 1QIQ 1QJE 1QJF
• Descriptor: ISOPENICILLIN N SYNTHASE, 6-(5-AMINO-5-CARBOXY-PENTANOYLAMINO)-3-HYDROXYMETHYL-7-OXO-4-THIA-1-AZA-BICYCLO[3.2.0]HEPTANE-2-CARBOXYLIC ACID, SULFATE ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, antibiotic biosynthesis, b-lactam antibiotic, oxygenase, penicillin biosynthesis
• Biological source: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
• Total number of polymer chains: 1
• Total formula weight: 38077.12

Authors

Elkins, J.M.,Rutledge, P.J.,Burzlaff, N.I.,Clifton, I.J.,Adlington, R.M.,Roach, P.L.,Baldwin, J.E. (deposition date: 2003-02-19, release date: 2003-06-19, Last modification date: 2024-05-08)

Primary citation

Elkins, J.M.,Rutledge, P.J.,Burzlaff, N.I.,Clifton, I.J.,Adlington, R.M.,Roach, P.L.,Baldwin, J.E.
Crystallographic Studies on the Reaction of Isopenicillin N Synthase with an Unsaturated Substrate Analogue
Org.Biomol.Chem., 1:1455-, 2003

PubMed Abstract: Isopenicillin N synthase (IPNS) catalyses conversion of the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N (IPN), the central step in biosynthesis of the beta-lactam antibiotics. The unsaturated substrate analogue delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-vinylglycine (ACvG) has previously been incubated with IPNS and single product was isolated, a 2-alpha-hydroxymethyl isopenicillin N (HMPen), formed via a monooxygenase mode of reactivity. ACvG has now been crystallised with IPNS and the structure of the anaerobic IPNS:Fe(II):ACvG complex determined to 1.15 A resolution. Furthermore, by exposing the anaerobically grown crystals to high-pressure oxygen gas, a structure corresponding to the bicyclic product HMPen has been obtained at 1.60 A resolution. In light of these and other IPNS structures, and recent developments with related dioxygenases, the [2 + 2] cycloaddition mechanism for HMPen formation from ACvG has been revised, and a stepwise radical mechanism is proposed. This revised mechanism remains consistent with the observed stereospecificity of the transformation, but fits better with apparent constraints on the coordination geometry around the active site iron atom.

PubMed: 12926272
DOI: 10.1039/B212270G

Experimental method

X-RAY DIFFRACTION (1.6 Å)