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Crystal structures and biochemical analyses of intermediate cleavage peptidase: role of dynamics in enzymatic function
Author(s) -
Singh Rahul,
Goyal Venuka Durani,
Kumar Ashwani,
Sabharwal Naripjeet Singh,
Makde Ravindra D.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13321
Subject(s) - dimer , protein data bank (rcsb pdb) , protein data bank , enzyme , chemistry , residue (chemistry) , monomer , cleavage (geology) , stereochemistry , protein structure , biochemistry , crystallography , biology , paleontology , organic chemistry , fracture (geology) , polymer
Intermediate cleavage peptidase (Icp55) processes a subset of mitochondrial matrix proteins by removing a bulky residue at their N termini, leaving behind smaller N-terminal residues (icp activity). This contributes towards the stability of the mitochondrial proteome. We report crystal structures of yeast Icp55 including one bound to the apstatin inhibitor. Apart from icp activity, the enzyme was found to exhibit Xaa-Pro aminopeptidase activity in vitro. Structural and biochemical data suggest that the enzyme exists in a rapid equilibrium between monomer and dimer. Furthermore, the dimer, and not the monomer, was found to be the active species with loop dynamics at the dimer interface playing an important role in activity. Based on the new evidence, we propose a model for binding and processing of cellular targets by Icp55. DATABASE: The atomic coordinates and structure factors for the structures of Icp55 (code 6A9T, 6A9U, 6A9V) have been deposited in the Protein Data Bank (PDB) (http://www.pdb.org/).