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| | ==Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-Aminomutase from Taxus chinensis== | | ==Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-Aminomutase from Taxus chinensis== |
| - | <StructureSection load='4c5s' size='340' side='right' caption='[[4c5s]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='4c5s' size='340' side='right'caption='[[4c5s]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c5s]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C5S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c5s]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Taxus_chinensis Taxus chinensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C5S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BQ7:(3S)-3-AMINO-2,2-DIFLUORO-3-PHENYLPROPANOIC+ACID'>BQ7</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MDO:{2-[(1S)-1-AMINOETHYL]-4-METHYLIDENE-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>MDO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BQ7:(3S)-3-AMINO-2,2-DIFLUORO-3-PHENYLPROPANOIC+ACID'>BQ7</scene>, <scene name='pdbligand=MDO:{2-[(1S)-1-AMINOETHYL]-4-METHYLIDENE-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>MDO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c5r|4c5r]], [[4c5t|4c5t]], [[4c5u|4c5u]], [[4c5v|4c5v]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c5s OCA], [https://pdbe.org/4c5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c5s RCSB], [https://www.ebi.ac.uk/pdbsum/4c5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c5s ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylalanine_ammonia-lyase Phenylalanine ammonia-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.1.24 4.3.1.24] </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=4c5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c5s OCA], [http://pdbe.org/4c5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c5s RCSB], [http://www.ebi.ac.uk/pdbsum/4c5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c5s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PAM_TAXWC PAM_TAXWC] Phenylalanine aminomutase that catalyzes the rearrangement of L-phenylalanine to R-beta-phenylalanine. Catalyzes the first commited step in the biosynthesis of the side chain of the alkaloid taxol (paclitaxel), a widely-used compound with antitumor activity. Has also low phenylalanine ammonia-lyase activity and can catalyze the amination of trans-cinnamate.<ref>PMID:15878763</ref> <ref>PMID:22113970</ref> <ref>PMID:24786474</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Aminomutase|Aminomutase]] | + | *[[Aminomutase 3D structures|Aminomutase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Phenylalanine ammonia-lyase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dijkstra, B W]] | + | [[Category: Taxus chinensis]] |
| - | [[Category: Feringa, B L]] | + | [[Category: Dijkstra BW]] |
| - | [[Category: Janssen, D B]] | + | [[Category: Feringa BL]] |
| - | [[Category: Szymanski, W]] | + | [[Category: Janssen DB]] |
| - | [[Category: Wu, B]] | + | [[Category: Szymanski W]] |
| - | [[Category: Wybenga, G G]] | + | [[Category: Wu B]] |
| - | [[Category: Lyase]]
| + | [[Category: Wybenga GG]] |
| - | [[Category: Methylidene-imidazole-5-one]]
| + | |
| - | [[Category: Y80a]]
| + | |
| Structural highlights
Function
PAM_TAXWC Phenylalanine aminomutase that catalyzes the rearrangement of L-phenylalanine to R-beta-phenylalanine. Catalyzes the first commited step in the biosynthesis of the side chain of the alkaloid taxol (paclitaxel), a widely-used compound with antitumor activity. Has also low phenylalanine ammonia-lyase activity and can catalyze the amination of trans-cinnamate.[1] [2] [3]
Publication Abstract from PubMed
Phenylalanine-2,3-aminomutase (PAM) from Taxus chinensis, a 4-methylidene-imidazole-5-one (MIO)-dependent enzyme, catalyzes the reversible conversion of (S)-alpha-phenylalanine into (R)-beta-phenylalanine via trans-cinnamic acid. The enzyme also catalyzes the direct addition of ammonia to trans-cinnamic acid, a reaction that can be used for the preparation of beta-amino acids, which occur as frequent constituents of bioactive compounds. Different hypotheses have been formulated to explain the stereochemistry of the PAM-catalyzed reaction, but structural evidence for these hypotheses is lacking. Furthermore, it remains unclear how the PAM MIO group is formed from the three-amino acid (A-S-G) sequence motif. For these reasons, we elucidated PAM three-dimensional (3D) structures with a bound (R)-beta-phenylalanine analogue and with bound trans-cinnamic acid. In addition, 3D structures of the (inactive) Y322A and N231A mutants of PAM were elucidated, which were found to be MIO-less. We conclude that the stereochemistry of the PAM-catalyzed reaction originates from the enzyme's ability to bind trans-cinnamic acid in two different orientations, with either the si,si face or the re,re face directed toward the MIO group, as evidenced by two distinct carboxylate binding modes. The results also suggest that the N231 side chain promotes MIO group formation by increasing the nucleophilicity of the G177 N atom through acidification of the amide proton.
Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-aminomutase from Taxus chinensis.,Wybenga GG, Szymanski W, Wu B, Feringa BL, Janssen DB, Dijkstra BW Biochemistry. 2014 May 12. PMID:24786474[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Steele CL, Chen Y, Dougherty BA, Li W, Hofstead S, Lam KS, Xing Z, Chiang SJ. Purification, cloning, and functional expression of phenylalanine aminomutase: the first committed step in Taxol side-chain biosynthesis. Arch Biochem Biophys. 2005 Jun 1;438(1):1-10. PMID:15878763 doi:http://dx.doi.org/10.1016/j.abb.2005.04.012
- ↑ Wu B, Szymanski W, Wybenga GG, Heberling MM, Bartsch S, de Wildeman S, Poelarends GJ, Feringa BL, Dijkstra BW, Janssen DB. Mechanism-inspired engineering of phenylalanine aminomutase for enhanced beta-regioselective asymmetric amination of cinnamates. Angew Chem Int Ed Engl. 2012 Jan 9;51(2):482-6. doi: 10.1002/anie.201106372. Epub, 2011 Nov 23. PMID:22113970 doi:http://dx.doi.org/10.1002/anie.201106372
- ↑ Wybenga GG, Szymanski W, Wu B, Feringa BL, Janssen DB, Dijkstra BW. Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-aminomutase from Taxus chinensis. Biochemistry. 2014 May 12. PMID:24786474 doi:http://dx.doi.org/10.1021/bi500187a
- ↑ Wybenga GG, Szymanski W, Wu B, Feringa BL, Janssen DB, Dijkstra BW. Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-aminomutase from Taxus chinensis. Biochemistry. 2014 May 12. PMID:24786474 doi:http://dx.doi.org/10.1021/bi500187a
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