|
| | | | |
| | | |
| Stat |
Members: 3645
Articles: 2'501'711
Articles rated: 2609
19 April 2024 |
|
| | | | |
|
Article overview
| |
|
|
Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation | | P L Roach
; I J Clifton
; C M Hensgens
; N Shibata
; C J Schofield
; J Hajdu
; J E Baldwin
; | | Date: |
19 Jun 1997 | | Journal: | Nature, 387 (6635), 827-30 | | Abstract: | The biosynthesis of penicillin and cephalosporin antibiotics in microorganisms requires the formation of the bicyclic nucleus of penicillin. Isopenicillin N synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the reaction of a tripeptide, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV), and dioxygen to form isopenicillin N and two water molecules. Mechanistic studies suggest the reaction is initiated by ligation of the substrate thiolate to the iron centre, and proceeds through an enzyme-bound monocyclic intermediate. Here we report the crystal structure of IPNS complexed to ferrous iron and ACV, determined to 1.3 A resolution. Based on the structure, we propose a mechanism for penicillin formation that involves ligation of ACV to the iron centre, creating a vacant iron coordination site into which dioxygen can bind. Subsequently, iron-dioxygen and iron-oxo species remove the requisite hydrogens from ACV without the direct assistance of protein residues. The crystal structure of the complex with the dioxygen analogue, NO and ACV bound to the active-site iron supports this hypothesis. | | Source: | PubMed, pmid9194566 doi: 10.1038/42990 | | Services: | Forum | Review | Favorites | |
|
|
No review found.
Did you like this article?
Note: answers to reviews or questions about the article must be posted in the forum section.
Authors are not allowed to review their own article. They can use the forum section.
browser Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)
|
| |
|
|
|
|
News, job offers and information for researchers and scientists:
| |
REGISTER