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4c5u

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Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-Aminomutase from Taxus chinensis

Structural highlights

4c5u is a 4 chain structure with sequence from Taxus chinensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.19Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4c5u"

@@ Line 1: / Line 1: @@
 ==Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-Aminomutase from Taxus chinensis==
-<StructureSection load='4c5u' size='340' side='right' caption='[[4c5u]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
+<StructureSection load='4c5u' size='340' side='right'caption='[[4c5u]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4c5u]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C5U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C5U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4c5u]] 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=4C5U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C5U FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c5r|4c5r]], [[4c5s|4c5s]], [[4c5t|4c5t]], [[4c5v|4c5v]]</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]] 2.19&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=4c5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c5u OCA], [https://pdbe.org/4c5u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c5u RCSB], [https://www.ebi.ac.uk/pdbsum/4c5u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c5u 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=4c5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c5u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c5u RCSB], [http://www.ebi.ac.uk/pdbsum/4c5u PDBsum]</span></td></tr>
 </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;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4c5u" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminomutase 3D structures|Aminomutase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </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: 4-methylidene-imidazole-5-one]]
+[[Category: Wybenga GG]]
-[[Category: Lyase]]

4c5u

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Current revision

Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-Aminomutase from Taxus chinensis

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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