5bu3
From Proteopedia
Crystal Structure of Diels-Alderase PyrI4 in complex with its product
Structural highlights
FunctionPYRI4_STRRG Involved in the biosynthesis of the spirotetramate antibiotics pyrroindomycins. Catalyzes the intramolecular cyclization forming the spiro-conjugate moiety in pyrroindomycins, via an exo-selective [4+2] cycloaddition reaction.[1] [2] Publication Abstract from PubMedThe Diels-Alder [4 + 2] cycloaddition reaction is one of the most powerful and elegant organic synthesis methods for forming 6-membered molecules and has been known for nearly a century. However, whether and how enzymes catalyze this type of reaction is still not completely clear. Here we focus on PyrI4, an enzyme found in the biosynthetic pathway of pyrroindomycins where it catalyzes the formation of a spiro-conjugate via an enzyme-dependent exo-selective [4 + 2] cycloaddition reaction. We report the crystal structures of PyrI4 alone and in complex with its product. Comparative analysis of these structures, combined with biochemical analysis, lead us to propose a unique trapping mechanism whereby the lid-like action of the N-terminal tail imposes conformational constraints on the beta barrel catalytic core, which enhances the proximity and polarization effects of reactive groups (1,3-diene and alkene) to drive cyclization in a regio- and stereo-specific manner. This work represents an important step toward the wider application of enzyme-catalyzed [4 + 2] cyclization for synthetic purposes. Enzyme-Dependent [4 + 2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4.,Zheng Q, Guo Y, Yang L, Zhao Z, Wu Z, Zhang H, Liu J, Cheng X, Wu J, Yang H, Jiang H, Pan L, Liu W Cell Chem Biol. 2016 Feb 8. pii: S2451-9456(16)30006-X. doi:, 10.1016/j.chembiol.2016.01.005. PMID:26877021[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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