1ips
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Penicillin antibiotics are all produced from fermentation-derived | + | Penicillin antibiotics are all produced from fermentation-derived penicillins because their chemical synthesis is not commercially viable. The key step in penicillin biosynthesis, in which both the beta-lactam and thiazolidine rings of the nucleus are created, is mediated by isopenicillin N synthase (IPNS), which binds ferrous iron and uses dioxygen as a cosubstrate. In a unique enzymatic step, with no chemical precedent, IPNS catalyses the transfer of four hydrogen atoms from its tripeptide substrate to dioxygen forming, in a single reaction, the complete bicyclic nucleus of the penicillins. We now report the structure of IPNS complexed with manganese, which reveals the active site is unusually buried within a 'jelly-roll' motif and lined by hydrophobic residues, and suggest how this structure permits the process of penicillin formation. Sequence analyses indicate IPNS, 1-aminocyclopropane-1-carboxylic acid oxidase and many of the 2-oxo-acid-dependent oxygenases contain a conserved jelly-roll motif, forming a new structural family of enzymes. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Andersson, I.]] | [[Category: Andersson, I.]] | ||
| - | [[Category: Baldwin, J | + | [[Category: Baldwin, J E.]] |
| - | [[Category: Barton, G | + | [[Category: Barton, G J.]] |
| - | [[Category: Clifton, I | + | [[Category: Clifton, I J.]] |
[[Category: Fulop, V.]] | [[Category: Fulop, V.]] | ||
[[Category: Hajdu, J.]] | [[Category: Hajdu, J.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
| - | [[Category: Roach, P | + | [[Category: Roach, P L.]] |
| - | [[Category: Schofield, C | + | [[Category: Schofield, C J.]] |
[[Category: MN]] | [[Category: MN]] | ||
[[Category: antibiotic biosynthesis]] | [[Category: antibiotic biosynthesis]] | ||
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[[Category: penicillin biosynthesis]] | [[Category: penicillin biosynthesis]] | ||
| - | ''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 13:14:22 2008'' |
Revision as of 11:14, 21 February 2008
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ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (MANGANESE COMPLEX)
Overview
Penicillin antibiotics are all produced from fermentation-derived penicillins because their chemical synthesis is not commercially viable. The key step in penicillin biosynthesis, in which both the beta-lactam and thiazolidine rings of the nucleus are created, is mediated by isopenicillin N synthase (IPNS), which binds ferrous iron and uses dioxygen as a cosubstrate. In a unique enzymatic step, with no chemical precedent, IPNS catalyses the transfer of four hydrogen atoms from its tripeptide substrate to dioxygen forming, in a single reaction, the complete bicyclic nucleus of the penicillins. We now report the structure of IPNS complexed with manganese, which reveals the active site is unusually buried within a 'jelly-roll' motif and lined by hydrophobic residues, and suggest how this structure permits the process of penicillin formation. Sequence analyses indicate IPNS, 1-aminocyclopropane-1-carboxylic acid oxidase and many of the 2-oxo-acid-dependent oxygenases contain a conserved jelly-roll motif, forming a new structural family of enzymes.
About this Structure
1IPS is a Single protein structure of sequence from Emericella nidulans with as ligand. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes., Roach PL, Clifton IJ, Fulop V, Harlos K, Barton GJ, Hajdu J, Andersson I, Schofield CJ, Baldwin JE, Nature. 1995 Jun 22;375(6533):700-4. PMID:7791906
Page seeded by OCA on Thu Feb 21 13:14:22 2008
