4hmv: Difference between revisions
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==Crystal structure of PhzG from Pseudomonas fluorescens 2-79 in complex with tetrahydrophenazine-1-carboxylic acid after 5 days of soaking== | |||
<StructureSection load='4hmv' size='340' side='right' caption='[[4hmv]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4hmv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HMV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HMV FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WUB:(1R,10AS)-1,2,10,10A-TETRAHYDROPHENAZINE-1-CARBOXYLIC+ACID'>WUB</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hms|4hms]], [[4hmt|4hmt]], [[4hmu|4hmu]], [[4hmw|4hmw]], [[4hmx|4hmx]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">phzG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hmv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hmv RCSB], [http://www.ebi.ac.uk/pdbsum/4hmv PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PHZG_PSEFL PHZG_PSEFL]] Involved in the biosynthesis of the antibiotic phenazine, a nitrogen-containing heterocyclic molecule having important roles in virulence, competition and biological control. Probably catalyzes the final step in the conversion of trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) to phenazine-1-carboxylic acid (PCA). | [[http://www.uniprot.org/uniprot/PHZG_PSEFL PHZG_PSEFL]] Involved in the biosynthesis of the antibiotic phenazine, a nitrogen-containing heterocyclic molecule having important roles in virulence, competition and biological control. Probably catalyzes the final step in the conversion of trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) to phenazine-1-carboxylic acid (PCA). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phenazines are redox-active secondary metabolites that many bacteria produce and secrete into the environment. They are broad-specificity antibiotics, but also act as virulence and survival factors in infectious diseases. Phenazines are derived from chorismic acid, but important details of their biosynthesis are still unclear. For example, three two-electron oxidations seem to be necessary in the final steps of the pathway, while only one oxidase, the FMN-dependent PhzG, is conserved in the phenazine-biosynthesis phz operon. Here, crystal structures of PhzG from Pseudomonas fluorescens 2-79 and from Burkholderia lata 383 in complex with excess FMN and with the phenazine-biosynthesis intermediates hexahydrophenazine-1,6-dicarboxylate and tetrahydrophenazine-1-carboxylate generated in situ are reported. Corroborated with biochemical data, these complexes demonstrate that PhzG is the terminal enzyme in phenazine biosynthesis and that its relaxed substrate specificity lets it participate in the generation of both phenazine-1,6-dicarboxylic acid (PDC) and phenazine-1-carboxylic acid (PCA). This suggests that competition between flavin-dependent oxidations through PhzG and spontaneous oxidative decarboxylations determines the ratio of PDC, PCA and unsubstituted phenazine as the products of phenazine biosynthesis. Further, the results indicate that PhzG synthesizes phenazines in their reduced form. These reduced molecules, and not the fully aromatized derivatives, are the likely end products in vivo, explaining why only one oxidase is required in the phenazine-biosynthesis pathway. | |||
Trapped intermediates in crystals of the FMN-dependent oxidase PhzG provide insight into the final steps of phenazine biosynthesis.,Xu N, Ahuja EG, Janning P, Mavrodi DV, Thomashow LS, Blankenfeldt W Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1403-13. doi:, 10.1107/S0907444913008354. Epub 2013 Jul 13. PMID:23897464<ref>PMID:23897464</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacillus fluorescens liquefaciens flugge 1886]] | [[Category: Bacillus fluorescens liquefaciens flugge 1886]] | ||
[[Category: Ahuja, E G | [[Category: Ahuja, E G]] | ||
[[Category: Blankenfeldt, W | [[Category: Blankenfeldt, W]] | ||
[[Category: Xu, N N | [[Category: Xu, N N]] | ||
[[Category: Decarboxylation]] | [[Category: Decarboxylation]] | ||
[[Category: Intermediate]] | [[Category: Intermediate]] |
Revision as of 22:09, 24 December 2014
Crystal structure of PhzG from Pseudomonas fluorescens 2-79 in complex with tetrahydrophenazine-1-carboxylic acid after 5 days of soakingCrystal structure of PhzG from Pseudomonas fluorescens 2-79 in complex with tetrahydrophenazine-1-carboxylic acid after 5 days of soaking
Structural highlights
Function[PHZG_PSEFL] Involved in the biosynthesis of the antibiotic phenazine, a nitrogen-containing heterocyclic molecule having important roles in virulence, competition and biological control. Probably catalyzes the final step in the conversion of trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) to phenazine-1-carboxylic acid (PCA). Publication Abstract from PubMedPhenazines are redox-active secondary metabolites that many bacteria produce and secrete into the environment. They are broad-specificity antibiotics, but also act as virulence and survival factors in infectious diseases. Phenazines are derived from chorismic acid, but important details of their biosynthesis are still unclear. For example, three two-electron oxidations seem to be necessary in the final steps of the pathway, while only one oxidase, the FMN-dependent PhzG, is conserved in the phenazine-biosynthesis phz operon. Here, crystal structures of PhzG from Pseudomonas fluorescens 2-79 and from Burkholderia lata 383 in complex with excess FMN and with the phenazine-biosynthesis intermediates hexahydrophenazine-1,6-dicarboxylate and tetrahydrophenazine-1-carboxylate generated in situ are reported. Corroborated with biochemical data, these complexes demonstrate that PhzG is the terminal enzyme in phenazine biosynthesis and that its relaxed substrate specificity lets it participate in the generation of both phenazine-1,6-dicarboxylic acid (PDC) and phenazine-1-carboxylic acid (PCA). This suggests that competition between flavin-dependent oxidations through PhzG and spontaneous oxidative decarboxylations determines the ratio of PDC, PCA and unsubstituted phenazine as the products of phenazine biosynthesis. Further, the results indicate that PhzG synthesizes phenazines in their reduced form. These reduced molecules, and not the fully aromatized derivatives, are the likely end products in vivo, explaining why only one oxidase is required in the phenazine-biosynthesis pathway. Trapped intermediates in crystals of the FMN-dependent oxidase PhzG provide insight into the final steps of phenazine biosynthesis.,Xu N, Ahuja EG, Janning P, Mavrodi DV, Thomashow LS, Blankenfeldt W Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1403-13. doi:, 10.1107/S0907444913008354. Epub 2013 Jul 13. PMID:23897464[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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