2VBD

Isopenicillin N synthase with substrate analogue L,L,L-ACOMP (unexposed)

Summary for 2VBD

• Entry DOI: 10.2210/pdb2vbd/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
• Descriptor: ISOPENICILLIN N SYNTHETASE, FE (II) ION, N^6^-[(1R)-2-[(1R)-1-carboxy-2-(methylsulfanyl)ethoxy]-2-oxo-1-(sulfanylmethyl)ethyl]-6-oxo-L-lysine, ... (4 entities in total)
• Functional Keywords: antibiotic biosynthesis, penicillin biosynthesis, iron, oxygenase, vitamin c, metal-binding, monocyclic intermediate, 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: 38002.13

Authors

Ge, W.,Clifton, I.J.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J. (deposition date: 2007-09-10, release date: 2008-09-23, Last modification date: 2024-05-08)

Primary citation

Ge, W.,Clifton, I.J.,Stok, J.E.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J.
The Crystal Structure of an Lll-Configured Depsipeptide Substrate Analogue Bound to Isopenicillin N Synthase.
Org.Biomol.Chem., 8:122-, 2010

PubMed Abstract: Isopenicillin N synthase (IPNS) is a non-heme iron(ii) oxidase, which catalyses the biosynthesis of isopenicillin N (IPN) from the tripeptide delta-l-alpha-aminoadipoyl-l-cysteinyl-d-valine (lld-ACV) in a remarkable oxidative bicyclisation reaction. The natural substrate for IPNS is the lld-configured tripeptide. lll-ACV is not turned over by the enzyme, but inhibits turnover of the lld-tripeptide. The mechanism by which this inhibition takes place is not fully understood. Recent studies have employed a range of lld-configured depsipeptide substrate analogues in crystallographic studies to probe events preceding beta-lactam closure in the IPNS reaction cycle. Herein, we report the first crystal structure of IPNS in complex with an lll-configured depsipeptide analogue, delta-l-alpha-aminoadipoyl-l-cysteine (1-(R)-carboxy-2-thiomethyl)ethyl ester (lll-ACOmC). This report describes the crystal structure of the IPNS:Fe(ii):lll-ACOmC complex to 2.0 A resolution, and discusses attempts to oxygenate this complex at high pressure in order to probe the mechanism by which lll-configured substrates inhibit IPNS catalysis.

PubMed: 20024142
DOI: 10.1039/B910170E

Experimental method

X-RAY DIFFRACTION (2 Å)