4o5t

Crystal structure of Diels-Alderase CE20 in complex with a product analog

spinqualitylabelsall models 4o5t, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4o5t is a 2 chain structure with sequence from Common european squid. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: XDA Related: 3u0s, 3i1c, 1e1a, 4o5s Activity: Diisopropyl-fluorophosphatase, with EC number 3.1.8.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DFPA_LOLVU] Biological function and substrate unknown. However, it is capable of acting on phosphorus anhydride bonds (such as phosphorus-halide and phosphorus-cyanide) in organophosphorus compounds (including nerve gases). Publication Abstract from PubMed By combining targeted mutagenesis, computational refinement, and directed evolution, a modestly active, computationally designed Diels-Alderase was converted into the most proficient biocatalyst for [4+2] cycloadditions known. The high stereoselectivity and minimal product inhibition of the evolved enzyme enabled preparative scale synthesis of a single product diastereomer. X-ray crystallography of the enzyme-product complex shows that the molecular changes introduced over the course of optimization, including addition of a lid structure, gradually reshaped the pocket for more effective substrate preorganization and transition state stabilization. The good overall agreement between the experimental structure and the original design model with respect to the orientations of both the bound product and the catalytic side chains contrasts with other computationally designed enzymes. Because design accuracy appears to correlate with scaffold rigidity, improved control over backbone conformation will likely be the key to future efforts to design more efficient enzymes for diverse chemical reactions. Impact of scaffold rigidity on the design and evolution of an artificial Diels-Alderase.,Preiswerk N, Beck T, Schulz JD, Milovnik P, Mayer C, Siegel JB, Baker D, Hilvert D Proc Natl Acad Sci U S A. 2014 May 20. pii: 201401073. PMID:24847076 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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