2Y60

Isopenicillin N synthase with AC-D-methionine

Summary for 2Y60

• Entry DOI: 10.2210/pdb2y60/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 2JB4 2VAU 2VBB 2VBD 2VBP 2VCM 2VE1 2WO7
• Descriptor: ISOPENICILLIN N SYNTHASE, N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-methionine, FE (III) ION, ... (6 entities in total)
• Functional Keywords: oxidoreductase, oxygenase, penicillin biosynthesis
• 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: 38299.40

Authors

Rutledge, P.J.,Clifton, I.J.,Ge, W. (deposition date: 2011-01-19, release date: 2012-02-08, Last modification date: 2024-05-08)

Primary citation

Clifton, I.J.,Ge, W.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J.
The Crystal Structure of Isopenicillin N Synthase with Delta((L)-Alpha-Aminoadipoyl)-(L)-Cysteinyl-(D)-Methionine Reveals Thioether Coordination to Iron.
Arch.Biochem.Biophys., 516:103-, 2011

PubMed Abstract: Isopenicillin N synthase (IPNS) catalyses cyclization of δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N (IPN), the central step in penicillin biosynthesis. Previous studies have shown that IPNS turns over a wide range of substrate analogues in which the valine residue of its natural substrate is replaced with other amino acids. IPNS accepts and oxidizes numerous substrates that bear hydrocarbon sidechains in this position, however the enzyme is less tolerant of analogues presenting polar functionality in place of the valinyl isopropyl group. We report a new ACV analogue δ-(l-α-aminoadipoyl)-l-cysteinyl-d-methionine (ACM), which incorporates a thioether in place of the valinyl sidechain. ACM has been synthesized using solution phase methods and crystallized with IPNS. A crystal structure has been elucidated for the IPNS:Fe(II):ACM complex at 1.40Å resolution. This structure reveals that ACM binds in the IPNS active site such that the sulfur atom of the methionine thioether binds to iron in the oxygen binding site at a distance of 2.57Å. The sulfur of the cysteinyl thiolate sits 2.36Å from the metal.

PubMed: 22001738
DOI: 10.1016/J.ABB.2011.09.014

Experimental method

X-RAY DIFFRACTION (1.4 Å)