1UZW

ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE

Summary for 1UZW

• Entry DOI: 10.2210/pdb1uzw/pdb
• Related: 1BK0 1BLZ 1HB1 1HB2 1HB3 1HB4 1IPS 1OBN 1OC1 1ODM 1ODN 1QIQ 1QJE 1QJF
• Descriptor: ISOPENICILLIN N SYNTHETASE, FE (II) ION, D-(L-A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE, ... (5 entities in total)
• Functional Keywords: b-lactam antibiotic, oxygenase, penicillin biosynthesis, antibiotic biosynthesis, oxidoreductase
• 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: 38077.16

Authors

Grummitt, A.R.,Rutledge, P.J.,Clifton, I.J.,Baldwin, J.E. (deposition date: 2004-03-17, release date: 2004-06-10, Last modification date: 2024-05-08)

Primary citation

Grummitt, A.R.,Rutledge, P.J.,Clifton, I.J.,Baldwin, J.E.
Active Site Mediated Elimination of Hydrogen Fluoride from a Fluorinated Substrate Analogue by Isopenicillin N Synthase
Biochem.J., 382:659-, 2004

PubMed Abstract: Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of bicyclic isopenicillin N from delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). In this study we report a novel activity for the iron of the IPNS active site, which behaves as a Lewis acid to catalyse the elimination of HF from the fluorinated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-beta-fluorovaline (ACbetaFV). X-Ray crystallographic studies of IPNS crystals grown anaerobically with ACbetaFV reveal that the valinyl beta-fluorine is missing from the active site region, and suggest the presence of the unsaturated tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-isodehydrovaline in place of substrate ACbetaFV. (19)F NMR studies confirm the release of fluoride from ACbetaFV in the presence of the active IPNS enzyme. These results suggest a new mode of reactivity for the IPNS iron centre, a mechanism of action that has not previously been reported for any of the iron oxidase enzymes.

PubMed: 15175003
DOI: 10.1042/BJ20040529

Experimental method

X-RAY DIFFRACTION (1.3 Å)