1odn
From Proteopedia
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ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN-EXPOSED PRODUCT FROM ANAEROBIC AC-VINYLGLYCINE FE COMPLEX)
Overview
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.
About this Structure
1ODN is a Single protein structure of sequence from Emericella nidulans with SO4, FE2 and APV as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystallographic studies on the reaction of isopenicillin N synthase with an unsaturated substrate analogue., Elkins JM, Rutledge PJ, Burzlaff NI, Clifton IJ, Adlington RM, Roach PL, Baldwin JE, Org Biomol Chem. 2003 May 7;1(9):1455-60. PMID:12926272
Page seeded by OCA on Tue Dec 18 17:33:34 2007
