Zvacek, Clemens and Friedrichs, Gerald and Heizinger, Leonhard and Merkl, Rainer (2015) An assessment of catalytic residue 3D ensembles for the prediction of enzyme function. BMC BIOINFORMATICS, 16: 359. ISSN 1471-2105,
Full text not available from this repository. (Request a copy)Abstract
Background: The central element of each enzyme is the catalytic site, which commonly catalyzes a single biochemical reaction with high specificity. It was unclear to us how often sites that catalyze the same or highly similar reactions evolved on different, i.e. non-homologous protein folds and how similar their 3D poses are. Both similarities are key criteria for assessing the usability of pose comparison for function prediction. Results: We have analyzed the SCOP database on the superfamily level in order to estimate the number of non-homologous enzymes possessing the same function according to their EC number. 89 % of the 873 substrate-specific functions (four digit EC number) assigned to mono-functional, single-domain enzymes were only found in one superfamily. For a reaction-specific grouping (three digit EC number), this value dropped to 35 %, indicating that in approximately 65 % of all enzymes the same function evolved in two or more non-homologous proteins. For these isofunctional enzymes, structural similarity of the catalytic sites may help to predict function, because neither high sequence similarity nor identical folds are required for a comparison. To assess the specificity of catalytic 3D poses, we compiled the redundancy-free set ENZ_SITES, which comprises 695 sites, whose composition and function are well-defined. We compared their poses with the help of the program Superpose3D and determined classification performance. If the sites were from different superfamilies, the number of true and false positive predictions was similarly high, both for a coarse and a detailed grouping of enzyme function. Moreover, classification performance did not improve drastically, if we additionally used homologous sites to predict function. Conclusions: For a large number of enzymatic functions, dissimilar sites evolved that catalyze the same reaction and it is the individual substrate that determines the arrangement of the catalytic site and its local environment. These substrate-specific requirements turn the comparison of catalytic residues into a weak classifier for the prediction of enzyme function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN FUNCTION; GENE ONTOLOGY; ACTIVE-SITES; ANNOTATION; EVOLUTION; CLASSIFICATION; SIMILARITY; TEMPLATES; HOMOLOGY; DATABASE; Catalytic site; Pose comparison; Enzyme function; Enzyme classification |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 11:25 |
| Last Modified: | 07 May 2019 11:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4475 |
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