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Biochemical and Docking Analysis of Polyisoprenylated Methylated Protein Methyl Esterase with Substrates
Author(s) -
Duverna Randolph,
Lamango Nazarius
Publication year - 2010
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.24.1_supplement.681.6
Subject(s) - chemistry , stereochemistry , in silico , esterase , enzyme , methylation , docking (animal) , affinities , substrate (aquarium) , biochemistry , binding affinities , prenylation , biology , receptor , medicine , ecology , nursing , gene
Polyisprenylated proteins (PP) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase), making it the only reversible step of the polyisoprenylation pathway. Since PMPMEase and PPMTase may influence both the structural and functional conformations of PP, a thorough study of these enzymes is essential to our understanding of the physiology of PP. PMPMEase has been reported under various pseudonyms because of its apparent broad substrate metabolism. The current study aimed to reveal its role as the endogenous polyisoprenylation‐specific esterase. A series of N‐, S‐ and O‐substituted substrates were analyzed by Michaelis‐Menten kinetics using porcine liver PMPMEase and in silico determination of binding affinities using Arguslab. Consistent with the biochemical analysis, the S‐ethyl analog yielded an AScore binding energy of −11.32 compared to −13.48, −14.88, −16.15 and −16.81 kcal/mol for S‐prenyl (C‐5), S‐trans‐geranyl (C‐10), S‐trans, trans‐farnesyl (C‐15) and S‐all trans‐geranylgeranyl (C‐20), respectively. As judged by the KM and AScore values, substrates with the natural modifications have the highest affinity for PMPMEase. The results demonstrate that PP are the likely endogenous substrates for PMPMEase.