2IVJ

Isopenicillin N Synthase From Aspergillus Nidulans (Anaerobic Ac- cyclopropylglycine Fe Complex)

Summary for 2IVJ

• Entry DOI: 10.2210/pdb2ivj/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
• Descriptor: ISOPENICILLIN N SYNTHETASE, D-(L-A-AMINOADIPOYL)-L-CYSTEINYL-D-CYCLOPROPYLGLYCINE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: antbiotic biosynthesis, antibiotic biosynthesis, iron, oxygenase, vitamin c, metal-binding, penicillin biosynthesis, 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: 38173.22

Authors

Howard-Jones, A.R.,Elkins, J.M.,Clifton, I.J.,Roach, P.L.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J. (deposition date: 2006-06-13, release date: 2007-04-10, Last modification date: 2024-05-08)

Primary citation

Howard-Jones, A.R.,Elkins, J.M.,Clifton, I.J.,Roach, P.L.,Adlington, R.M.,Baldwin, J.E.,Rutledge, P.J.
Interactions of Isopenicillin N Synthase with Cyclopropyl-Containing Substrate Analogues Reveal New Mechanistic Insight.
Biochemistry, 46:4755-, 2007

PubMed Abstract: 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.

PubMed: 17397141
DOI: 10.1021/BI062314Q

Experimental method

X-RAY DIFFRACTION (1.46 Å)