Structure of a cephalosporin synthase

Karin Valegård, Anke C. Terwisscha van Scheltinga, Matthew D. Lloyd, Takane Hara, S. Ramaswamy, Anastassis Perrakis, Andy Thompson, Hwei-Jen Lee, Jack E. Baldwin, Christopher J. Schofield (), Janos Hajdu and Inger Andersson ()
Additional contact information
Karin Valegård: Uppsala University
Anke C. Terwisscha van Scheltinga: Swedish University of Agricultural Sciences
Matthew D. Lloyd: Oxford Centre for Molecular Sciences and Dyson Perrins Laboratory, Oxford University
Takane Hara: Uppsala University
S. Ramaswamy: Swedish University of Agricultural Sciences
Anastassis Perrakis: EMBL Grenoble
Andy Thompson: EMBL Grenoble
Hwei-Jen Lee: Oxford Centre for Molecular Sciences and Dyson Perrins Laboratory, Oxford University
Jack E. Baldwin: Oxford Centre for Molecular Sciences and Dyson Perrins Laboratory, Oxford University
Christopher J. Schofield: Oxford Centre for Molecular Sciences and Dyson Perrins Laboratory, Oxford University
Janos Hajdu: Uppsala University
Inger Andersson: Swedish University of Agricultural Sciences

Nature, 1998, vol. 394, issue 6695, 805-809

Abstract: Abstract Penicillins and cephalosporins are among the most widely used therapeutic agents. These antibiotics are produced from fermentation-derived materials as their chemical synthesis is not commercially viable. Unconventional steps in their biosynthesis are catalysed by Fe(II)-dependent oxidases/oxygenases; isopenicillin N synthase (IPNS)1,2 creates in one step the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is produced by the oxidative splitting of a co-substrate, 2-oxoglutarate (α-ketoglutarate). This route of controlled ferryl formation and reaction is common to many mononuclear ferrous enzymes3, which participate in a broader range of reactions than their well-characterized counterparts, the haem enzymes. Here we report the first crystal structure of a 2-oxoacid-dependent oxygenase. High-resolution structures for apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a model based on these structures, we propose a mechanism for ferryl formation.

Date: 1998
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/29575 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:394:y:1998:i:6695:d:10.1038_29575

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/29575

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().