The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms

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Beyer , H M , Virtanen , S , Aranko , A S , Mikula , K M , Lountos , G T , Wlodawer , A , Ollila , O H S & Iwai , H 2020 , ' The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms ' , International Journal of Molecular Sciences , vol. 21 , no. 21 , 8367 . https://doi.org/10.3390/ijms21218367

Title: The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms
Author: Beyer, Hannes M.; Virtanen, Salla; Aranko, A. Sesilja; Mikula, Kornelia M.; Lountos, George T.; Wlodawer, Alexander; Ollila, O.H. Samuli; Iwai, Hideo
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Biophysical chemistry
University of Helsinki, Institute of Biotechnology
Date: 2020-11
Language: eng
Number of pages: 20
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
URI: http://hdl.handle.net/10138/322662
Abstract: 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.
Subject: protein-splicing mechanism
intein
protein engineering
protein evolution
protease
FULLY-AUTOMATIC CHARACTERIZATION
PARTICLE MESH EWALD
CRYSTAL-STRUCTURE
DATA-COLLECTION
STRUCTURAL BASIS
INTEIN
EVOLUTION
DOMAIN
CHYMOTRYPSIN
REFINEMENT
1182 Biochemistry, cell and molecular biology
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