4c5s | pdb_00004c5s

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

spinqualitylabelsall models 4c5s, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c5s 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 1.85Å Ligands: BQ7, MDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAM_TAXCH 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. Has also low phenylalanine ammonia-lyase activity and can catalyze the amination of trans-cinnamate. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminomutase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA