2jb4
From Proteopedia
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==Overview== | ==Overview== | ||
| - | A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) | + | A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the central enzyme in the biosynthesis of penicillin antibiotics. The crystal structure of the IPNS-cyclobutanone complex reveals an active site environment similar to that seen in the enzyme-product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS-cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. Furthermore, the successful cocrystallisation of this analogue with IPNS provides firm structural evidence for the utility of such cyclobutanone derivatives as hydrolytically stable analogues of bicyclic beta-lactams. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | A | + | A cyclobutanone analogue mimics penicillin in binding to isopenicillin N synthase., Stewart AC, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ, Chembiochem. 2007 Nov 5;8(16):2003-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17907118 17907118] |
[[Category: Emericella nidulans]] | [[Category: Emericella nidulans]] | ||
[[Category: Isopenicillin-N synthase]] | [[Category: Isopenicillin-N synthase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Adlington, R | + | [[Category: Adlington, R M.]] |
| - | [[Category: Baldwin, J | + | [[Category: Baldwin, J E.]] |
| - | [[Category: Clifton, I | + | [[Category: Clifton, I J.]] |
| - | [[Category: Rutledge, P | + | [[Category: Rutledge, P J.]] |
| - | [[Category: Stewart, A | + | [[Category: Stewart, A C.]] |
[[Category: A14]] | [[Category: A14]] | ||
[[Category: FE]] | [[Category: FE]] | ||
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[[Category: vitamin c]] | [[Category: vitamin c]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:01:23 2008'' |
Revision as of 16:01, 21 February 2008
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ISOPENICILLIN N SYNTHASE WITH A 2-THIABICYCLOHEPTAN-6-ONE PRODUCT ANALOGUE
Overview
A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the central enzyme in the biosynthesis of penicillin antibiotics. The crystal structure of the IPNS-cyclobutanone complex reveals an active site environment similar to that seen in the enzyme-product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS-cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. Furthermore, the successful cocrystallisation of this analogue with IPNS provides firm structural evidence for the utility of such cyclobutanone derivatives as hydrolytically stable analogues of bicyclic beta-lactams.
About this Structure
2JB4 is a Single protein structure of sequence from Emericella nidulans with , , and as ligands. Active as Isopenicillin-N synthase, with EC number 1.21.3.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
A cyclobutanone analogue mimics penicillin in binding to isopenicillin N synthase., Stewart AC, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ, Chembiochem. 2007 Nov 5;8(16):2003-7. PMID:17907118
Page seeded by OCA on Thu Feb 21 18:01:23 2008
Categories: Emericella nidulans | Isopenicillin-N synthase | Single protein | Adlington, R M. | Baldwin, J E. | Clifton, I J. | Rutledge, P J. | Stewart, A C. | A14 | FE | GOL | SO4 | Antibiotic biosynthesis | B-lactam antibiotic | Iron | Metal-binding | Oxidoreductase | Oxygenase | Penicillin biosynthesis | Vitamin c
