2vaq

STRUCTURE OF STRICTOSIDINE SYNTHASE IN COMPLEX WITH INHIBITOR

spinqualitylabelsall models 2vaq, resolution 3.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vaq is a 2 chain structure with sequence from Ophioxylon serpentinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: VAW Related: 2fp8, 2fp9, 2fpb, 2v91, 2fpc Activity: Strictosidine synthase, with EC number 4.3.3.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [STSY_RAUSE] Catalyzes the stereospecific condensation of tryptamine with secologanin to form strictosidine, the key intermediate of indole alkaloid biosynthesis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The Pictet-Spengler reaction, which yields either a beta-carboline or a tetrahydroquinoline product from an aromatic amine and an aldehyde, is widely utilized in plant alkaloid biosynthesis. Here we deconvolute the role that the biosynthetic enzyme strictosidine synthase plays in catalyzing the stereoselective synthesis of a beta-carboline product. Notably, the rate-controlling step of the enzyme mechanism, as identified by the appearance of a primary kinetic isotope effect (KIE), is the rearomatization of a positively charged intermediate. The KIE of a nonenzymatic Pictet-Spengler reaction indicates that rearomatization is also rate-controlling in solution, suggesting that the enzyme does not significantly change the mechanism of the reaction. Additionally, the pH dependence of the solution and enzymatic reactions provides evidence for a sequence of acid-base catalysis steps that catalyze the Pictet-Spengler reaction. An additional acid-catalyzed step, most likely protonation of a carbinolamine intermediate, is also significantly rate controlling. We propose that this step is efficiently catalyzed by the enzyme. Structural analysis of a bisubstrate inhibitor bound to the enzyme suggests that the active site is exquisitely tuned to correctly orient the iminium intermediate for productive cyclization to form the diastereoselective product. Furthermore, ab initio calculations suggest the structures of possible productive transition states involved in the mechanism. Importantly, these calculations suggest that a spiroindolenine intermediate, often invoked in the Pictet-Spengler mechanism, does not occur. A detailed mechanism for enzymatic catalysis of the beta-carboline product is proposed from these data. Strictosidine synthase: mechanism of a Pictet-Spengler catalyzing enzyme.,Maresh JJ, Giddings LA, Friedrich A, Loris EA, Panjikar S, Trout BL, Stockigt J, Peters B, O'Connor SE J Am Chem Soc. 2008 Jan 16;130(2):710-23. PMID:18081287 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Strictosidine Synthase

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