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Evolution of chalco...
Evolution of chalcone isomerase from a noncatalytic ancestor
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- Kaltenbach, Miriam (author)
- Weizmann Inst Sci, Dept Biol Chem, Rehovot, Israel
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- Burke, Jason R. (author)
- Salk Inst Biol Studies, Howard Hughes Med Inst, Jack H Skirball Ctr Chem Biol & Prote, La Jolla, CA 92037 USA
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- Dindo, Mirco (author)
- Weizmann Inst Sci, Dept Biol Chem, Rehovot, Israel;Univ Verona, Biol Chem Sect, Dept Neurosci Biomed & Movement Sci, Verona, Italy
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- Pabis, Anna (author)
- Uppsala universitet,Molekylär biofysik
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- Steffen-Munsberg, Fabian (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Rabin, Avigayel (author)
- Weizmann Inst Sci, Dept Biol Chem, Rehovot, Israel;Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, Edmond J Safra Campus, Jerusalem, Israel
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- Kamerlin, Shina C. Lynn, 1981- (author)
- Uppsala universitet,Strukturbiologi
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- Noel, Joseph P. (author)
- Salk Inst Biol Studies, Howard Hughes Med Inst, Jack H Skirball Ctr Chem Biol & Prote, La Jolla, CA 92037 USA
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- Tawfik, Dan S. (author)
- Weizmann Inst Sci, Dept Biol Chem, Rehovot, Israel
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(creator_code:org_t)
- 2018-04-23
- 2018
- English.
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In: Nature Chemical Biology. - : NATURE PUBLISHING GROUP. - 1552-4450 .- 1552-4469. ; 14:6, s. 548-555
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 substratebinding mode and repositioning of the catalytic arginine that was inherited from the ancestral fatty-acid binding proteins.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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