4v2q

Ironing out their differences: Dissecting the structural determinants of a phenylalanine aminomutase and ammonia lyase

spinqualitylabelsall models 4v2q, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4v2q is a 2 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 1.95Å Ligands: 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 Deciphering the structural features that functionally separate ammonia lyases from aminomutases is of interest because it may allow for the engineering of more efficient aminomutases for the synthesis of unnatural amino acids (e.g., beta-amino acids). However, this has proved to be a major challenge that involves understanding the factors that influence their activity and regioselectivity differences. Herein, we report evidence of a structural determinant that dictates the activity differences between a phenylalanine ammonia lyase (PAL) and aminomutase (PAM). An inner loop region that closes the active sites of both PAM and PAL was mutated within PAM (PAM residues 77-97) in a step-wise approach to study the effects when the equivalent residue(s) found in the PAL loop were introduced into the PAM loop. Almost all of the single loop mutations triggered a lyase phenotype in PAM. Experimental and computational evidence suggest that the induced lyase features result from inner loop mobility enhancements, which are possibly caused by a 310-helix cluster, flanking alpha-helices, and hydrophobic interactions. These findings pinpoint the inner loop as a structural determinant of the lyase and mutase activities of PAM. Ironing out their differences: Dissecting the structural determinants of a phenylalanine aminomutase and ammonia lyase.,Heberling MM, Masman MF, Bartsch S, Wybenga GG, Dijkstra BW, Marrink SJ, Janssen DB ACS Chem Biol. 2014 Dec 10. PMID:25494407 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminomutase 3D structures

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