Divergence and Convergence in Enzyme Evolution

作者: Michael Y. Galperin , Eugene V. Koonin

DOI: 10.1074/JBC.R111.241976

关键词: Sequence analysisComputational biologyGeneticsActive siteEntatic stateSequence motifBiologyHydrolaseConserved sequenceGeneEnzyme structure

摘要: Comparative analysis of the sequences enzymes encoded in a variety prokaryotic and eukaryotic genomes reveals convergence divergence at several levels. Functional can be inferred when structurally distinct hence non-homologous show ability to catalyze same biochemical reaction. In contrast, as result functional diversification, many similar enzyme molecules act on substantially substrates diverse reactions. Here, we present updates ATP-grasp, alkaline phosphatase, cupin, HD hydrolase, N-terminal nucleophile (Ntn) hydrolase superfamilies discuss patterns sequence structural conservation diversity within these superfamilies. Typically, superfamily possess common motifs key active site residues, well (predicted) reaction mechanisms. These observations suggest that strained conformation (the entatic state) site, which is responsible for substrate binding formation transition complex, tends conserved The subsequent fate complex not necessarily depends details structures substrate. This variability outcomes limits predict exact enzymatic activities newly sequenced gene products. Nevertheless, sequence-based (super)family assignments generic predictions, even if imprecise, provide valuable leads experimental studies remain best approach annotation uncharacterized proteins from new genomes.

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