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| [[Image:2bnn.gif|left|200px]] | | {{Seed}} |
| | [[Image:2bnn.png|left|200px]] |
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| {{STRUCTURE_2bnn| PDB=2bnn | SCENE= }} | | {{STRUCTURE_2bnn| PDB=2bnn | SCENE= }} |
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| '''STRUCTURE OF A ZN ENZYME'''
| | ===STRUCTURE OF A ZN ENZYME=== |
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| ==Overview==
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| The biosynthesis of fosfomycin, an oxirane antibiotic in clinical use, involves a unique epoxidation catalyzed by (S)-2-hydroxypropylphosphonic acid epoxidase (HPPE). The reaction is essentially dehydrogenation of a secondary alcohol. A high-resolution crystallographic analysis reveals that the HPPE subunit displays a two-domain combination. The C-terminal or catalytic domain has the cupin fold that binds a divalent cation, whereas the N-terminal domain carries a helix-turn-helix motif with putative DNA-binding helices positioned 34 A apart. The structure of HPPE serves as a model for numerous proteins, of ill-defined function, predicted to be transcription factors but carrying a cupin domain at the C terminus. Structure-reactivity analyses reveal conformational changes near the catalytic center driven by the presence or absence of ligand, that HPPE is a Zn(2+)/Fe(2+)-dependent epoxidase, proof that flavin mononucleotide is required for catalysis, and allow us to propose a simple mechanism that is compatible with previous experimental data. The participation of the redox inert Zn(2+) in the mechanism is surprising and indicates that Lewis acid properties of the metal ions are sufficient to polarize the substrate and, aided by flavin mononucleotide reduction, facilitate the epoxidation. | | The line below this paragraph, {{ABSTRACT_PUBMED_16186494}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16186494 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16186494}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Epoxidase,cupin,hth,cation-dependant]] | | [[Category: Epoxidase,cupin,hth,cation-dependant]] |
| [[Category: Zinc,fosfomycin oxidoreductase]] | | [[Category: Zinc,fosfomycin oxidoreductase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:32:10 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:45:03 2008'' |
