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Understanding How Distal Residues Play a Role in Parkin Activity
Author(s) -
Winters Jenifer,
Beuning Penny,
Makowski Lee,
Ondrechen Mary Jo
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.654.7
Subject(s) - parkin , ubiquitin ligase , mutagenesis , ubiquitin , chemistry , enzyme , biochemistry , mutation , site directed mutagenesis , proteasome , microbiology and biotechnology , biophysics , biology , parkinson's disease , disease , mutant , gene , medicine , pathology
Partial Order Optimum Likelihood (POOL) is a machine learning method that predicts catalytically important residues based on the tertiary structure of the protein, with computed chemical and electrostatic properties of the residues as input features. POOL has predicted spatially extended active sites, where residues that are not in direct contact with the substrate still contribute to catalysis for many enzymes, including for parkin. Parkin is an E3 ubiquitin ligase protein involved in the ubiquitin‐proteosome system that mediates the targeting of proteins for degradation. Mutations in parkin lead to the accumulation of toxic substrates that damage dopaminergic neurons, causing the autosomal recessive form of Parkinson's disease (PD). POOL has predicted a dozen residues in parkin that are important for catalytic activity. Interestingly, half of these residues are positions that when mutated lead to the onset of PD. Enzyme variants were created through single‐site directed mutagenesis to further look into how these residues may play a role in catalysis through biochemical and biophysical techniques. Support or Funding Information Supported by NSF MCB‐1517290 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .