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Publication Abstract from PubMed

Tryptophan synthase (TrpS) is a heterotetrameric alphabetabetaalpha enzyme that exhibits complex substrate channeling and allosteric mechanisms and is a model system in enzymology. In this work, we characterize proposed early and late evolutionary states of TrpS and show that they have distinct quaternary structures, caused by insertions-deletions of sequence segments (indels) in the beta-subunit. Remarkably, indole hydrophobic channels that connect alpha and beta active sites have re-emerged in both TrpS types, yet they follow different paths through the beta-subunit fold. Also, both TrpS geometries activate the alpha-subunit through the rearrangement of loops flanking the active site. Our results link evolutionary sequence changes in the enzyme subunits with channeling and allostery in the TrpS enzymes. The findings demonstrate that indels allow protein quaternary architectures to scape "minima" in the evolutionary landscape, thereby overcoming the conservational constraints imposed by existing functional interfaces and being free to morph into new mechanistic enzymes.

Evolutionary Morphing of Tryptophan Synthase: Functional Mechanisms for the Enzymatic Channeling of Indole.,Fleming JR, Schupfner M, Busch F, Basle A, Ehrmann A, Sterner R, Mayans O J Mol Biol. 2018 Oct 24. pii: S0022-2836(18)30606-5. doi:, 10.1016/j.jmb.2018.10.013. PMID:30367843^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.