2JB4

Isopenicillin N synthase with a 2-thiabicycloheptan-6-one product analogue

Summary for 2JB4

• Entry DOI: 10.2210/pdb2jb4/pdb
• Related: 1BK0 1BLZ 1HB1 1HB2 1HB3 1HB4 1IPS 1OBN 1OC1 1ODM 1ODN 1QIQ 1QJE 1QJF 1UZW 1W03 1W04 1W05 1W06 1W3V 1W3X 2BJS 2BU9 2IVI 2IVJ
• Descriptor: Isopenicillin N synthase, (1S,4S,5S,7R)-7-{[(5S)-5-AMINO-5-CARBOXYPENTANOYL]AMINO}-3,3-DIMETHYL-6-OXO-2-THIABICYCLO[3.2.0]HEPTANE-4-CARBOXYLIC ACID, FE (III) ION, ... (6 entities in total)
• Functional Keywords: antibiotic biosynthesis, penicillin biosynthesis, iron, oxygenase, vitamin c, metal-binding, oxidoreductase, b-lactam antibiotic
• 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: 38262.31

Authors

Stewart, A.C.,Clifton, I.J.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J. (deposition date: 2006-12-01, release date: 2007-10-16, Last modification date: 2024-05-08)

Primary citation

Stewart, A.C.,Clifton, I.J.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J.
A Cyclobutanone Analogue Mimics Penicillin in Binding to Isopenicillin N Synthase.
Chembiochem, 8:2003-, 2007

PubMed Abstract: A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the central enzyme in the biosynthesis of penicillin antibiotics. The crystal structure of the IPNS-cyclobutanone complex reveals an active site environment similar to that seen in the enzyme-product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS-cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. Furthermore, the successful cocrystallisation of this analogue with IPNS provides firm structural evidence for the utility of such cyclobutanone derivatives as hydrolytically stable analogues of bicyclic beta-lactams.

PubMed: 17907118
DOI: 10.1002/CBIC.200700176

Experimental method

X-RAY DIFFRACTION (1.3 Å)