2y60

Isopenicillin N synthase with AC-D-methionineIsopenicillin N synthase with AC-D-methionine

Structural highlights 2y60 is a 1 chain structure with sequence from Aspergillus nidulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IPNA_EMENI Isopenicillin N synthase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:3319778, PubMed:11755401). IpnA catalyzes the cyclization of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) to form isopenicillin N (IPN) that contains the beta-lactam nucleus (PubMed:3319778, PubMed:11755401, PubMed:28703303). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity).[UniProtKB:P08703] Publication Abstract from PubMed Isopenicillin N synthase (IPNS) catalyses cyclization of delta-(l-alpha-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 delta-(l-alpha-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 1.40A 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 2.57A. The sulfur of the cysteinyl thiolate sits 2.36A from the metal. The crystal structure of isopenicillin N synthase with delta-((L)-alpha-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron.,Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ Arch Biochem Biophys. 2011 Dec 15;516(2):103-7. doi: 10.1016/j.abb.2011.09.014., Epub 2011 Oct 6. PMID:22001738 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isopenicillin N synthase

spinqualitylabelsall models 2y60, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image