1yyq

Y305F Trichodiene Synthase complexed with pyrophosphateY305F Trichodiene Synthase complexed with pyrophosphate

Structural highlights 1yyq is a 2 chain structure with sequence from Fusarium sporotrichioides. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRI5_FUSSP TS is a member of the terpene cyclase group of enzymes. It catalyzes the isomerization and cyclization of farnesyl pyro-phosphate to form trichodiene, the first cyclic intermediate in the biosynthetic pathway for trichothecenes. It serves to branch trichothecene biosynthesis from the isoprenoid pathway. 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 X-ray crystal structures of Y305F trichodiene synthase and its complex with coproduct inorganic pyrophosphate (PP(i)) and of Y305F and D100E trichodiene synthases in ternary complexes with PP(i) and aza analogues of the bisabolyl carbocation intermediate are reported. The Y305F substitution in the basic D(302)RRYR motif does not cause large changes in the overall structure in comparison with the wild-type enzyme in either the uncomplexed enzyme or its complex with PP(i). However, the loss of the Y305F-PP(i) hydrogen bond appears to be compensated by a very slight shift in the position of the side chain of R304. The putative bisabolyl carbocation mimic, R-azabisabolene, binds in a conformation and orientation that does not appear to mimic that of the actual carbocation intermediate, suggesting that the avid inhibition by R- and S-azabisabolenes arises more from favorable electrostatic interactions with PP(i) rather than any special resemblance to a reaction intermediate. Greater enclosed active-site volumes result from the Y305F and D100E mutations that appear to confer greater variability in ligand-binding conformations and orientations, which results in the formation of aberrant cyclization products. Because the binding conformations and orientations of R-azabisabolene to Y305F and D100E trichodiene synthases do not correspond to binding conformations required for product formation and because the binding conformations and orientations of diverse substrate and carbocation analogues to other cyclases such as 5-epi-aristolochene synthase and bornyl diphosphate synthase generally do not correspond to catalytically productive complexes, we conclude that the formation of transient carbocation intermediates in terpene cyclization reactions is generally under kinetic rather than thermodynamic control. Molecular recognition of the substrate diphosphate group governs product diversity in trichodiene synthase mutants.,Vedula LS, Rynkiewicz MJ, Pyun HJ, Coates RM, Cane DE, Christianson DW Biochemistry. 2005 Apr 26;44(16):6153-63. PMID:15835903 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Trichodiene synthase

spinqualitylabelsall models 1yyq, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image