2V91

STRUCTURE OF STRICTOSIDINE SYNTHASE IN COMPLEX WITH STRICTOSIDINE

Summary for 2V91

• Entry DOI: 10.2210/pdb2v91/pdb
• Related: 2FP8 2FP9 2FPB 2FPC 2VAQ
• Descriptor: STRICTOSIDINE SYNTHASE, METHYL (2S,3R,4S)-3-ETHYL-2-(BETA-D-GLUCOPYRANOSYLOXY)-4-[(1S)-2,3,4,9-TETRAHYDRO-1H-BETA-CARBOLIN-1-YLMETHYL]-3,4-DIHYDRO-2H-PYRAN-5-CARBOXYLATE (3 entities in total)
• Functional Keywords: alkaloid metabolism, six bladed beta propeller fold, str1, lyase, vacuole, synthase, glycoprotein
• Biological source: RAUVOLFIA SERPENTINA (SERPENTWOOD)
• Total number of polymer chains: 2
• Total formula weight: 68452.37

Authors

Loris, E.A.,Panjikar, S.,Ruppert, M.,Barleben, L.,Unger, M.,Stoeckigt, J. (deposition date: 2007-08-16, release date: 2008-09-16, Last modification date: 2024-11-06)

Primary citation

Loris, E.A.,Panjikar, S.,Ruppert, M.,Barleben, L.,Unger, M.,Schubel, H.,Stoeckigt, J.
Structure Based Engineering of Strictosidine Synthase: Auxiliary for Alkaloid Libraries
Chem.Biol., 14:979-, 2007

PubMed Abstract: The highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented.

PubMed: 17884630
DOI: 10.1016/J.CHEMBIOL.2007.08.009

Experimental method

X-RAY DIFFRACTION (3.01 Å)