6evf: Difference between revisions
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<StructureSection load='6evf' size='340' side='right' caption='[[6evf]], [[Resolution|resolution]] 2.06Å' scene=''> | <StructureSection load='6evf' size='340' side='right' caption='[[6evf]], [[Resolution|resolution]] 2.06Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6evf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EVF FirstGlance]. <br> | <table><tr><td colspan='2'>[[6evf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EVF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4LU:1-DEOXY-5-O-PHOSPHONO-1-(3,3,4,5-TETRAMETHYL-9,11-DIOXO-2,3,8,9,10,11-HEXAHYDRO-7H-QUINOLINO[1,8-FG]PTERIDIN-12-IUM-7-YL)-D-RIBITOL'>4LU</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4LU:1-DEOXY-5-O-PHOSPHONO-1-(3,3,4,5-TETRAMETHYL-9,11-DIOXO-2,3,8,9,10,11-HEXAHYDRO-7H-QUINOLINO[1,8-FG]PTERIDIN-12-IUM-7-YL)-D-RIBITOL'>4LU</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FDC1, YDR539W, D3703.2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenacrylate_decarboxylase Phenacrylate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.102 4.1.1.102] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenacrylate_decarboxylase Phenacrylate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.102 4.1.1.102] </span></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=6evf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evf OCA], [http://pdbe.org/6evf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6evf RCSB], [http://www.ebi.ac.uk/pdbsum/6evf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6evf ProSAT]</span></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=6evf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evf OCA], [http://pdbe.org/6evf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6evf RCSB], [http://www.ebi.ac.uk/pdbsum/6evf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6evf ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FDC1_YEAST FDC1_YEAST]] Required for the decarboxylation of phenylacrylic acids like ferulic acid, p-coumaric acid or cinnamic acid. Not essential for ubiquinone synthesis.<ref>PMID:20471595</ref> | [[http://www.uniprot.org/uniprot/FDC1_YEAST FDC1_YEAST]] Required for the decarboxylation of phenylacrylic acids like ferulic acid, p-coumaric acid or cinnamic acid. Not essential for ubiquinone synthesis.<ref>PMID:20471595</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The UbiD family of reversible decarboxylases act on aromatic, heteroaromatic, and unsaturated aliphatic acids and utilize a prenylated flavin mononucleotide (prFMN) as cofactor, bound adjacent to a conserved Glu-ArgGlu/Asp ionic network in the enzyme's active site. It is proposed that UbiD activation requires oxidative maturation of the cofactor, for which two distinct isomers, prFMN(ketimine) and prFMN(iminium) have been observed. It also has been suggested that only the prFMN(iminium) form is relevant to catalysis, which requires transient cycloaddition between substrate and cofactor. Using Aspergillus niger Fdc1 as a model system, we reveal isomerization of prFMN(iminium) to prFMN(ketimine) is a light-dependent process that is largely independent of the Glu277-Arg173-Glu282 network and accompanied by irreversible loss of activity. On the other hand, efficient catalysis was highly dependent on an intact Glu-Ar-Glu network, as only Glu to Asp substitutions retain activity. Surprisingly, oxidative maturation to form the prFMN(iminium) species is severely affected only for the R173A variant. In summary, the unusual irreversible isomerization of prFMN is light dependent and likely proceeds via high-energy intermediates, but is independent of the Glu-Arg-Glu network. Our results from mutagenesis, crystallographic, spectroscopic and kinetic experiments indicate a clear role for the Glu-Arg-Glu network in both catalysis and oxidative maturation. | |||
The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerisation and catalysis.,Bailey SS, Payne KAP, Fisher K, Marshall SA, Cliff MJ, Spiess R, Parker DA, Rigby SE, Leys D J Biol Chem. 2017 Dec 19. pii: RA117.000881. doi: 10.1074/jbc.RA117.000881. PMID:29259125<ref>PMID:29259125</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6evf" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Baker's yeast]] | |||
[[Category: Phenacrylate decarboxylase]] | [[Category: Phenacrylate decarboxylase]] | ||
[[Category: Bailey, S S]] | [[Category: Bailey, S S]] | ||
Latest revision as of 09:06, 3 January 2018
Structure of E285D S. cerevisiae Fdc1 with prFMN in the hydroxylated formStructure of E285D S. cerevisiae Fdc1 with prFMN in the hydroxylated form
Structural highlights
Function[FDC1_YEAST] Required for the decarboxylation of phenylacrylic acids like ferulic acid, p-coumaric acid or cinnamic acid. Not essential for ubiquinone synthesis.[1] Publication Abstract from PubMedThe UbiD family of reversible decarboxylases act on aromatic, heteroaromatic, and unsaturated aliphatic acids and utilize a prenylated flavin mononucleotide (prFMN) as cofactor, bound adjacent to a conserved Glu-ArgGlu/Asp ionic network in the enzyme's active site. It is proposed that UbiD activation requires oxidative maturation of the cofactor, for which two distinct isomers, prFMN(ketimine) and prFMN(iminium) have been observed. It also has been suggested that only the prFMN(iminium) form is relevant to catalysis, which requires transient cycloaddition between substrate and cofactor. Using Aspergillus niger Fdc1 as a model system, we reveal isomerization of prFMN(iminium) to prFMN(ketimine) is a light-dependent process that is largely independent of the Glu277-Arg173-Glu282 network and accompanied by irreversible loss of activity. On the other hand, efficient catalysis was highly dependent on an intact Glu-Ar-Glu network, as only Glu to Asp substitutions retain activity. Surprisingly, oxidative maturation to form the prFMN(iminium) species is severely affected only for the R173A variant. In summary, the unusual irreversible isomerization of prFMN is light dependent and likely proceeds via high-energy intermediates, but is independent of the Glu-Arg-Glu network. Our results from mutagenesis, crystallographic, spectroscopic and kinetic experiments indicate a clear role for the Glu-Arg-Glu network in both catalysis and oxidative maturation. The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerisation and catalysis.,Bailey SS, Payne KAP, Fisher K, Marshall SA, Cliff MJ, Spiess R, Parker DA, Rigby SE, Leys D J Biol Chem. 2017 Dec 19. pii: RA117.000881. doi: 10.1074/jbc.RA117.000881. PMID:29259125[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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