1xua
From Proteopedia
(New page: 200px<br /><applet load="1xua" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xua, resolution 1.90Å" /> '''Structure and functi...) |
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| - | [[Image:1xua.jpg|left|200px]]<br /><applet load="1xua" size=" | + | [[Image:1xua.jpg|left|200px]]<br /><applet load="1xua" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xua, resolution 1.90Å" /> | caption="1xua, resolution 1.90Å" /> | ||
'''Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens'''<br /> | '''Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Phenazines produced by Pseudomonas and Streptomyces spp. are heterocyclic | + | Phenazines produced by Pseudomonas and Streptomyces spp. are heterocyclic nitrogen-containing metabolites with antibiotic, antitumor, and antiparasitic activity. The antibiotic properties of pyocyanin, produced by Pseudomonas aeruginosa, were recognized in the 1890s, although this blue phenazine is now known to be a virulence factor in human disease. Despite their biological significance, the biosynthesis of phenazines is not fully understood. Here we present structural and functional studies of PhzF, an enzyme essential for phenazine synthesis in Pseudomonas spp. PhzF shares topology with diaminopimelate epimerase DapF but lacks the same catalytic residues. The structure of PhzF in complex with its substrate, trans-2,3-dihydro-3-hydroxyanthranilic acid, suggests that it is an isomerase using the conserved glutamate E45 to abstract a proton from C3 of the substrate. The proton is returned to C1 of the substrate after rearrangement of the double-bond system, yielding an enol that converts to the corresponding ketone. PhzF is a dimer that may be bifunctional, providing a shielded cavity for ketone dimerization via double Schiff-base formation to produce the phenazine scaffold. Our proposed mechanism is supported by mass and NMR spectroscopy. The results are discussed in the context of related structures and protein sequences of unknown biochemical function. |
==About this Structure== | ==About this Structure== | ||
| - | 1XUA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens] with HHA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1XUA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens] with <scene name='pdbligand=HHA:'>HHA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XUA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Janning, P.]] | [[Category: Janning, P.]] | ||
[[Category: Korniyenko, Y.]] | [[Category: Korniyenko, Y.]] | ||
| - | [[Category: Kuzin, A | + | [[Category: Kuzin, A P.]] |
| - | [[Category: Mavrodi, D | + | [[Category: Mavrodi, D V.]] |
[[Category: Skarina, T.]] | [[Category: Skarina, T.]] | ||
| - | [[Category: Thomashow, L | + | [[Category: Thomashow, L S.]] |
[[Category: Tong, L.]] | [[Category: Tong, L.]] | ||
[[Category: HHA]] | [[Category: HHA]] | ||
[[Category: phenazine biosynthesis]] | [[Category: phenazine biosynthesis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:58:43 2008'' |
Revision as of 13:58, 21 February 2008
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Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens
Overview
Phenazines produced by Pseudomonas and Streptomyces spp. are heterocyclic nitrogen-containing metabolites with antibiotic, antitumor, and antiparasitic activity. The antibiotic properties of pyocyanin, produced by Pseudomonas aeruginosa, were recognized in the 1890s, although this blue phenazine is now known to be a virulence factor in human disease. Despite their biological significance, the biosynthesis of phenazines is not fully understood. Here we present structural and functional studies of PhzF, an enzyme essential for phenazine synthesis in Pseudomonas spp. PhzF shares topology with diaminopimelate epimerase DapF but lacks the same catalytic residues. The structure of PhzF in complex with its substrate, trans-2,3-dihydro-3-hydroxyanthranilic acid, suggests that it is an isomerase using the conserved glutamate E45 to abstract a proton from C3 of the substrate. The proton is returned to C1 of the substrate after rearrangement of the double-bond system, yielding an enol that converts to the corresponding ketone. PhzF is a dimer that may be bifunctional, providing a shielded cavity for ketone dimerization via double Schiff-base formation to produce the phenazine scaffold. Our proposed mechanism is supported by mass and NMR spectroscopy. The results are discussed in the context of related structures and protein sequences of unknown biochemical function.
About this Structure
1XUA is a Single protein structure of sequence from Pseudomonas fluorescens with as ligand. Full crystallographic information is available from OCA.
Reference
Structure and function of the phenazine biosynthetic protein PhzF from Pseudomonas fluorescens., Blankenfeldt W, Kuzin AP, Skarina T, Korniyenko Y, Tong L, Bayer P, Janning P, Thomashow LS, Mavrodi DV, Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16431-6. Epub 2004 Nov 15. PMID:15545603
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