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Publication Abstract from PubMed

Protein splicing catalyzed by inteins utilizes many different combinations of amino-acid types at active sites. Inteins have been classified into three classes based on their characteristic sequences. We investigated the structural basis of the protein splicing mechanism of class 3 inteins by determining crystal structures of variants of a class 3 intein from Mycobacterium chimaera and molecular dynamics simulations, which suggested that the class 3 intein utilizes a different splicing mechanism from that of class 1 and 2 inteins. The class 3 intein uses a bond cleavage strategy reminiscent of proteases but share the same Hedgehog/INTein (HINT) fold of other intein classes. Engineering of class 3 inteins from a class 1 intein indicated that a class 3 intein would unlikely evolve directly from a class 1 or 2 intein. The HINT fold appears as structural and functional solution for trans-peptidyl and trans-esterification reactions commonly exploited by diverse mechanisms using different combinations of amino-acid types for the active-site residues.

The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms.,Beyer HM, Virtanen SI, Aranko AS, Mikula KM, Lountos GT, Wlodawer A, Ollila OHS, Iwai H Int J Mol Sci. 2020 Nov 7;21(21). pii: ijms21218367. doi: 10.3390/ijms21218367. PMID:33171880^[1]

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