The structure of Rauvolfia serpentina strictosidine synthase is a novel six-bladed beta-propeller fold in plant proteins.
The enzyme strictosidine synthase (STR1) from the Indian medicinal plant Rauvolfia serpentina is of primary importance for the biosynthetic pathway of the indole alkaloid ajmaline. Moreover, STR1 initiates all biosynthetic pathways leading to the entire monoterpenoid indole alkaloid family representing an enormous structural variety of approximately 2000 compounds in higher plants. The crystal structures of STR1 in complex with its natural substrates tryptamine and secologanin provide structural understanding of the observed substrate preference and identify residues lining the active site surface that contact the substrates. STR1 catalyzes a Pictet-Spengler-type reaction and represents a novel six-bladed beta-propeller fold in plant proteins. Structure-based sequence alignment revealed a common repetitive sequence motif (three hydrophobic residues are followed by a small residue and a hydrophilic residue), indicating a possible evolutionary relationship between STR1 and several sequence-unrelated six-bladed beta-propeller structures. Structural analysis and site-directed mutagenesis experiments demonstrate the essential role of Glu-309 in catalysis. The data will aid in deciphering the details of the reaction mechanism of STR1 as well as other members of this enzyme family.
Department of Pharmaceutical Biology, Institute of Pharmacy, Johanes Gutenberg-University, D-55099 Mainz, Germany.
Xueyan
X
Ma
Santosh
S
Panjikar
Juergen
J
Koepke
Elke
E
Loris
Joachim
J
Stöckigt
D000595:Amino Acid Sequence; D001665:Binding Sites; D019759:Carbon-Nitrogen Lyases / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D017124:Conserved Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011926:Rauwolfia / Q000201:enzymology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014363:Tryptamines / Q000378:metabolism
D010940:Plant Proteins; D014363:Tryptamines; C030820:tryptamine; D019759:Carbon-Nitrogen Lyases; C022684:strictosidine synthetase