| Structural highlights
2ivj is a 1 chain structure with sequence from A. nidulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| 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 |
| Activity: | Isopenicillin-N synthase, with EC number 1.21.3.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[IPNS_EMENI] Removes, in the presence of oxygen, 4 hydrogen atoms from delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to form the azetidinone and thiazolidine rings of isopenicillin.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Isopenicillin N synthase (IPNS), a non-heme iron oxidase central to penicillin and cephalosporin biosynthesis, catalyzes an energetically demanding chemical transformation to produce isopenicillin N from the tripeptide delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV). We describe the synthesis of two cyclopropyl-containing tripeptide analogues, delta-(l-alpha-aminoadipoyl)-l-cysteinyl-beta-methyl-d-cyclopropylglycine and delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-cyclopropylglycine, designed as probes for the mechanism of IPNS. We have solved the X-ray crystal structures of these substrates in complex with IPNS and propose a revised mechanism for the IPNS-mediated turnover of these compounds. Relative to the previously determined IPNS-Fe(II)-ACV structure, key differences exist in substrate orientation and water occupancy, which allow for an explanation of the differences in reactivity of these substrates.
Interactions of isopenicillin N synthase with cyclopropyl-containing substrate analogues reveal new mechanistic insight.,Howard-Jones AR, Elkins JM, Clifton IJ, Roach PL, Adlington RM, Baldwin JE, Rutledge PJ Biochemistry. 2007 Apr 24;46(16):4755-62. Epub 2007 Mar 31. PMID:17397141[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Howard-Jones AR, Elkins JM, Clifton IJ, Roach PL, Adlington RM, Baldwin JE, Rutledge PJ. Interactions of isopenicillin N synthase with cyclopropyl-containing substrate analogues reveal new mechanistic insight. Biochemistry. 2007 Apr 24;46(16):4755-62. Epub 2007 Mar 31. PMID:17397141 doi:10.1021/bi062314q
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