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Publication Abstract from PubMed

The FK506-binding protein (FKBP) family of peptidyl prolyl isomerases (PPIases) is characterized by a common catalytic domain that binds to the inhibitors FK506 and rapamycin. As one of four FKBPs within the yeast Saccharomyces cerevisiae, Fpr4 has been described as a histone chaperone, and is in addition implicated in epigenetic function in part due to its mediation of cis-trans conversion of proline residues within histone tails. To better understand the molecular details of this activity, we have determined the solution structure of the Fpr4 C-terminal PPIase domain by using NMR spectroscopy. This canonical FKBP domain actively increases the rate of isomerization of three decapeptides derived from the N-terminus of yeast histone H3, while maintaining intrinsic cis and trans populations. Observation of the uncatalyzed and Fpr4-catalyzed isomerization rates at equilibrium demonstrate Pro16 and Pro30 of histone H3 as the major proline targets of Fpr4, with little activity shown against Pro38. This alternate ranking of the three target prolines, as compared to affinity determination or the classical chymotrypsin-based fluorescent assay, reveals the mechanistic importance of substrate residues C-terminal to the peptidyl-prolyl bond.

Structure and activity of the peptidyl-prolyl isomerase domain from the histone chaperone Fpr4 towards histone H3 proline isomerization.,Monneau YR, Soufari H, Nelson CJ, Mackereth CD J Biol Chem. 2013 Jul 25. PMID:23888048^[1]

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