6EEQ

Crystal structure of Rhodiola rosea 4-hydroxyphenylacetaldehyde synthase

Summary for 6EEQ

• Entry DOI: 10.2210/pdb6eeq/pdb
• Related: 6EEI 6EEM 6EEW
• Descriptor: 4-hydroxyphenylacetaldehyde synthase (2 entities in total)
• Functional Keywords: aromatic amino acid decarboxylase, lyase
• Biological source: Rhodiola rosea (Roseroot)
• Total number of polymer chains: 1
• Total formula weight: 54660.30

Authors

Torrens-Spence, M.P.,Chiang, Y.,Smith, T.,Vicent, M.A.,Wang, Y.,Weng, J.K. (deposition date: 2018-08-15, release date: 2018-09-19, Last modification date: 2025-04-02)

Primary citation

Torrens-Spence, M.P.,Chiang, Y.C.,Smith, T.,Vicent, M.A.,Wang, Y.,Weng, J.K.
Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins.
Proc.Natl.Acad.Sci.USA, 117:10806-10817, 2020

PubMed Abstract: Radiation of the plant pyridoxal 5'-phosphate (PLP)-dependent aromatic l-amino acid decarboxylase (AAAD) family has yielded an array of paralogous enzymes exhibiting divergent substrate preferences and catalytic mechanisms. Plant AAADs catalyze either the decarboxylation or decarboxylation-dependent oxidative deamination of aromatic l-amino acids to produce aromatic monoamines or aromatic acetaldehydes, respectively. These compounds serve as key precursors for the biosynthesis of several important classes of plant natural products, including indole alkaloids, benzylisoquinoline alkaloids, hydroxycinnamic acid amides, phenylacetaldehyde-derived floral volatiles, and tyrosol derivatives. Here, we present the crystal structures of four functionally distinct plant AAAD paralogs. Through structural and functional analyses, we identify variable structural features of the substrate-binding pocket that underlie the divergent evolution of substrate selectivity toward indole, phenyl, or hydroxyphenyl amino acids in plant AAADs. Moreover, we describe two mechanistic classes of independently arising mutations in AAAD paralogs leading to the convergent evolution of the derived aldehyde synthase activity. Applying knowledge learned from this study, we successfully engineered a shortened benzylisoquinoline alkaloid pathway to produce (S)-norcoclaurine in yeast. This work highlights the pliability of the AAAD fold that allows change of substrate selectivity and access to alternative catalytic mechanisms with only a few mutations.

PubMed: 32371491
DOI: 10.1073/pnas.1920097117

Experimental method

X-RAY DIFFRACTION (2.60008608017 Å)