{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:04:43Z","timestamp":1791576283148,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2021,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Isopenicillin\u2005N synthase (IPNS) is a non\u2010heme iron oxidase (NHIO) that catalyses the cyclisation of tripeptide \u03b4\u2010(\n                    <jats:sc>l<\/jats:sc>\n                    \u2010\u03b1\u2010aminoadipoyl)\u2010\n                    <jats:sc>l<\/jats:sc>\n                    \u2010cysteinyl\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010valine (ACV) to bicyclic isopenicillin\u2005N (IPN). Over the last 25\u2005years, crystallography has shed considerable light on the mechanism of IPNS catalysis. The first crystal structure, for apo\u2010IPNS with Mn bound in place of Fe at the active site, reported in 1995, was also the first structure for a member of the wider NHIO family. This was followed by the anaerobic enzyme\u2010substrate complex IPNS\u2212Fe\u2212ACV (1997), this complex plus nitric oxide as a surrogate for co\u2010substrate dioxygen (1997), and an enzyme product complex (1999). Since then, crystallography has been used to probe many aspects of the IPNS reaction mechanism, by crystallising the protein with a diversity of substrate analogues and triggering the oxidative reaction by using elevated oxygen pressures to force the gaseous co\u2010substrate throughout protein crystals and maximise synchronicity of turnover\n                    <jats:italic>in crystallo<\/jats:italic>\n                    . In this way, X\u2010ray structures have been elucidated for a range of complexes closely related to and\/or directly derived from key intermediates in the catalytic cycle, thereby answering numerous mechanistic questions that had arisen from solution\u2010phase experiments, and posing many new ones. The results of these crystallographic studies have, in turn, informed computational experiments that have brought further insight. These combined crystallographic and computational investigations augment and extend the results of earlier spectroscopic analyses and solution phase studies of IPNS turnover, to enrich our understanding of this important protein and the wider NHIO enzyme family.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202000743","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T18:34:48Z","timestamp":1610476488000},"page":"1687-1705","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Isopenicillin\u2005N Synthase: Crystallographic Studies"],"prefix":"10.1002","volume":"22","author":[{"given":"Nicole C.","family":"Chapman","sequence":"first","affiliation":[{"name":"School of Chemistry The University of Sydney  Sydney New South Wales 2006 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-5196","authenticated-orcid":false,"given":"Peter J.","family":"Rutledge","sequence":"additional","affiliation":[{"name":"School of Chemistry The University of Sydney  Sydney New South Wales 2006 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