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Review
. 2012 Jan 2;287(1):21-28.
doi: 10.1074/jbc.R111.241976. Epub 2011 Nov 8.

Divergence and convergence in enzyme evolution

Michael Y Galperin  1 , Eugene V Koonin  2
Affiliations
Review

Divergence and convergence in enzyme evolution

Michael Y Galperin et al. J Biol Chem. .

Abstract

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

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Figures

FIGURE 1.
FIGURE 1.
Conservation of structural core and active site residues in ATP-grasp (A), AlkP (B), cupin (C), and HD phosphohydrolase (D) superfamily enzymes. Conserved structural elements, identified through VAST alignments (83), are shown in tan, active site residues are shown as sticks, the most conserved residues are shown in bright colors (with carbon atoms shown in green), and catalytic metal atoms are shown as pink spheres. A, inositol-1,3,4-trisphosphate 5/6-kinase (Protein Data Bank code 1z2p (29)) with bound ATP analog AMP-PCP. Carbon atoms are in silver. B, AlkP(H331Q) mutant with a phosphoserine intermediate (code 1hjk (84)). C, cysteine dioxygenase with a persulfenate intermediate (code 3eln (85)). D, 5′-deoxyribonucleotidase with bound dAMP (code 2pau (50)).
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