5WL3

Crystal structure of chalcone isomerase engineered from ancestral inference (ancR2)

Summary for 5WL3

• Entry DOI: 10.2210/pdb5wl3/pdb
• Descriptor: Engineered Chalcone Isomerase ancR2, CHLORIDE ION (3 entities in total)
• Functional Keywords: chalcone isomerase, naringenin, flavanone, isomerase
• Biological source: unidentified
• Total number of polymer chains: 4
• Total formula weight: 95994.21

Authors

Burke, J.R.,Kaltenbach, M.,Tawfik, D.S.,Noel, J.P. (deposition date: 2017-07-25, release date: 2018-05-09, Last modification date: 2023-10-04)

Primary citation

Kaltenbach, M.,Burke, J.R.,Dindo, M.,Pabis, A.,Munsberg, F.S.,Rabin, A.,Kamerlin, S.C.L.,Noel, J.P.,Tawfik, D.S.
Evolution of chalcone isomerase from a noncatalytic ancestor.
Nat. Chem. Biol., 14:548-555, 2018

PubMed Abstract: 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.

PubMed: 29686356
DOI: 10.1038/s41589-018-0042-3

Experimental method

X-RAY DIFFRACTION (2.4 Å)