2bno: Difference between revisions

Revision as of 17:39, 21 February 2008

STRUCTURE OF A ZN ENZYME

OverviewOverview

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.

About this StructureAbout this Structure

2BNO is a Single protein structure of sequence from Streptomyces wedmorensis with , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Structure and reactivity of hydroxypropylphosphonic acid epoxidase in fosfomycin biosynthesis by a cation- and flavin-dependent mechanism., McLuskey K, Cameron S, Hammerschmidt F, Hunter WN, Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14221-6. Epub 2005 Sep 26. PMID:16186494

Page seeded by OCA on Thu Feb 21 16:39:41 2008

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OCA

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 ==Overview==
-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 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.
 ==About this Structure==
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 [[Category: Streptomyces wedmorensis]]
 [[Category: Cameron, S.]]
-[[Category: Hunter, W.N.]]
+[[Category: Hunter, W N.]]
 [[Category: Mcluskey, K.]]
 [[Category: HG]]
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 [[Category: zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:26:09 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:39:41 2008''