Received September 16, 2005
Returned for revision December 25, 2005
Accepted February 6, 2006
The Structure of Rauvolfia serpentina Strictosidine Synthase Is a Novel Six-Bladed 
-Propeller Fold in Plant Proteins
Xueyan Ma 1, Santosh Panjikar 2, Juergen Koepke 3, Elke Loris 1, and Joachim Stöckigt 4*
1 Department of Pharmaceutical Biology, Institute of Pharmacy, Johannes Gutenberg-University, D-55099 Mainz, Germany
2 European Molecular Biology Laboratory Hamburg Outstation DESY, D-22603 Hamburg, Germany
3 Department of Molecular Membrane Biology, Max-Planck-Institute of Biophysics, 60438 Frankfurt, Germany
4 Department of Pharmaceutical Biology, Institute of Pharmacy, Johannes Gutenberg-University, D-55099 Mainz, Germany; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China
* To whom correspondence should be addressed. E-mail: stoeckig{at}mail.uni-mainz.de.
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 
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 
-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 -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.
