6a9u
Crystal strcture of Icp55 from Saccharomyces cerevisiae bound to apstatin inhibitor
Structural highlights
FunctionICP55_YEAST Aminopeptidase which cleaves preprotein intermediates that carry destabilizing N-ter amino acid residues after the mitochondrial processing peptidase (MPP) cleavage site and is thus critical for stabilization of the mitochondrial proteome.[1] [2] Publication Abstract from PubMedIntermediate 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) (https://www.pdb.org/). Crystal structures and biochemical analyses of intermediate cleavage peptidase: role of dynamics in enzymatic function.,Singh R, Goyal VD, Kumar A, Sabharwal NS, Makde RD FEBS Lett. 2018 Dec 24. doi: 10.1002/1873-3468.13321. PMID:30582634[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
