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| | ==Crystal Structure of a Taxus Phenylalanine Aminomutase== | | ==Crystal Structure of a Taxus Phenylalanine Aminomutase== |
| - | <StructureSection load='3nz4' size='340' side='right' caption='[[3nz4]], [[Resolution|resolution]] 2.38Å' scene=''> | + | <StructureSection load='3nz4' size='340' side='right'caption='[[3nz4]], [[Resolution|resolution]] 2.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nz4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Taxus_canadensis Taxus canadensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NZ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NZ4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nz4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Taxus_canadensis Taxus canadensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NZ4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TCA:PHENYLETHYLENECARBOXYLIC+ACID'>TCA</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]] 2.38Å</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=MDO:{2-[(1S)-1-AMINOETHYL]-4-METHYLIDENE-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>MDO</scene>, <scene name='pdbligand=TCA:PHENYLETHYLENECARBOXYLIC+ACID'>TCA</scene></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=3nz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nz4 OCA], [https://pdbe.org/3nz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nz4 RCSB], [https://www.ebi.ac.uk/pdbsum/3nz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nz4 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=3nz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nz4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nz4 RCSB], [http://www.ebi.ac.uk/pdbsum/3nz4 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PAM_TAXCA PAM_TAXCA] Phenylalanine aminomutase that catalyzes the rearrangement of L-phenylalanine to R-beta-phenylalanine. Catalyzes the first committed step in the biosynthesis of the side chain of the alkaloid taxol (paclitaxel), a widely-used compound with antitumor activity. Also has low phenylalanine ammonia-lyase activity.<ref>PMID:21361343</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3nz4" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminomutase 3D structures|Aminomutase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Phenylalanine ammonia-lyase]] | + | [[Category: Large Structures]] |
| | [[Category: Taxus canadensis]] | | [[Category: Taxus canadensis]] |
| - | [[Category: Feng, L]] | + | [[Category: Feng L]] |
| - | [[Category: Geiger, J H]] | + | [[Category: Geiger JH]] |
| - | [[Category: Aminomutase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Mio]]
| + | |
| - | [[Category: Phenylalanine]]
| + | |
| - | [[Category: Taxol biosynthetic pathway]]
| + | |
| Structural highlights
Function
PAM_TAXCA Phenylalanine aminomutase that catalyzes the rearrangement of L-phenylalanine to R-beta-phenylalanine. Catalyzes the first committed step in the biosynthesis of the side chain of the alkaloid taxol (paclitaxel), a widely-used compound with antitumor activity. Also has low phenylalanine ammonia-lyase activity.[1]
Publication Abstract from PubMed
The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 A resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-alpha-phenylalanine to the (R)-beta-isomer by exchange of the NH(2)/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-beta-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition, the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-beta-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C(1)-C(alpha) and C(ipso)-C(beta) bonds 180 degrees in the active site prior to exchange and rebinding of the NH(2)/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an approximately 1.5-fold increase in k(cat) and a decrease in K(M) values for sterically demanding 3'-methyl-alpha-phenylalanine and styryl-alpha-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-alpha-phenylalanine compared to those for TcPAM.
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase.,Feng L, Wanninayake U, Strom S, Geiger J, Walker KD Biochemistry. 2011 Mar 21. PMID:21361343[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Feng L, Wanninayake U, Strom S, Geiger J, Walker KD. Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase. Biochemistry. 2011 Mar 21. PMID:21361343 doi:10.1021/bi102067r
- ↑ Feng L, Wanninayake U, Strom S, Geiger J, Walker KD. Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase. Biochemistry. 2011 Mar 21. PMID:21361343 doi:10.1021/bi102067r
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