Structural highlights
Function
[IPNS_EMENI] Removes, in the presence of oxygen, 4 hydrogen atoms from delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to form the azetidinone and thiazolidine rings of isopenicillin.
Publication Abstract from PubMed
Isopenicillin N synthase (IPNS) is a non-heme iron oxidase central to the biosynthesis of beta-lactam antibiotics. IPNS converts the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N while reducing molecular oxygen to water. The substrate analogue delta-(L-alpha-aminoadipoyl)-L-cysteinyl-O-methyl-D-threonine (ACmT) is not turned over by IPNS. Epimeric delta-(L-alpha-aminoadipoyl)-L-cysteinyl-O-methyl-D-allo-threonine (ACmaT) is converted to a bioactive penam product. ACmT and ACmaT differ from each other only in the stereochemistry at the beta-carbon atom of their third residue. These substrates both contain a methyl ether in place of the isopropyl group of ACV. We report an X-ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. This structure reveals an additional water molecule bound to the active site metal, held by hydrogen-bonding to the ether oxygen atom of the substrate analogue.
The crystal structure of an isopenicillin N synthase complex with an ethereal substrate analogue reveals water in the oxygen binding site.,Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ FEBS Lett. 2013 Aug 19;587(16):2705-9. doi: 10.1016/j.febslet.2013.07.016. Epub, 2013 Jul 13. PMID:23860486[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ. The crystal structure of an isopenicillin N synthase complex with an ethereal substrate analogue reveals water in the oxygen binding site. FEBS Lett. 2013 Aug 19;587(16):2705-9. doi: 10.1016/j.febslet.2013.07.016. Epub, 2013 Jul 13. PMID:23860486 doi:http://dx.doi.org/10.1016/j.febslet.2013.07.016
