5wkr

Crystal structure of chalcone isomerase engineered from ancestral inference complexed with naringenin (ancCC)

spinqualitylabelsall models 5wkr, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wkr is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, MPD, NAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable. Despite strong epistasis in other cases of protein evolution, CHI's laboratory reconstructed mutational trajectory shows weak epistasis. Thus, enantioselective CHI activity could readily emerge despite a catalytically inactive starting point. Accordingly, X-ray crystallography, NMR, and molecular dynamics simulations reveal reshaping of the active site toward a productive substrate-binding mode and repositioning of the catalytic arginine that was inherited from the ancestral fatty-acid binding proteins. Evolution of chalcone isomerase from a noncatalytic ancestor.,Kaltenbach M, Burke JR, Dindo M, Pabis A, Munsberg FS, Rabin A, Kamerlin SCL, Noel JP, Tawfik DS Nat Chem Biol. 2018 Apr 23. pii: 10.1038/s41589-018-0042-3. doi:, 10.1038/s41589-018-0042-3. PMID:29686356 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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