Divergence and Convergence in Enzyme Evolution

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.

Molecular recognition with boronic acids—applications in chemical biology

“…The binding sites of proteinsmade up of amino acid residues and other species such as metal ions-have evolved for highly specific and often very strong interactions with their target molecule and are therefore useful biochemical tools [11,21,70]. Biological receptors such as protein domains are often used as probes for the detection of their target molecule; one example is the use of antibodies to probe antigens in enzyme-linked immunosorbent assays (ELISA) [29].…”

Organophosphonate-degrading PhnZ reveals an emerging family of HD domain mixed-valent diiron oxygenases

“…. .D sequence motif that binds a divalent metal ion (often Zn II , Mg II , or Mn II ) (5). HD proteins with a dinuclear metal cluster, in which two additional histidines from within the D. .…”

“….D region of the domain form a second metal binding site, have also been identified (6,7). Only a limited number of HD proteins have been biochemically characterized; they almost exclusively catalyze phosphoester hydrolysis, which has led to the general assignment of HD proteins as phosphohydrolases (3,5,(8)(9)(10)(11)(12). The wide phylogenetic distribution and diverse domain architectures of the HD proteins suggest, however, that additional activities might have evolved within the superfamily.…”

Molecular homology and multiple-sequence alignment: an analysis of concepts and practice

“…Similarly, the roles of convergent evolution and chance in producing similarity of amino acid sequences has long been recognised (e.g. Doolittle 1981;Simmons 2000;Galperin and Koonin 2012), as has the disconnection between gene homology and the control of morphological development (de Beer 1971;Meyer 1999;Wagner 2014). But in terms of the body of literature, the identity of nucleotides in a set of coding or non-coding DNA sequences has been a poor cousin, largely relegated to an ostensible role in computerised sequence alignment.…”

“…For example, the genes encoding many biomolecular systems and pathways are genomically organised in operons or gene clusters, and this arrangement can be used as evidence for gene homology (Medema et al 2013). For molecules, it is commonly assumed that conservation of structure and function is more common than is convergence (this is almost a phenetic argument; Pavlinov 2012), although this always needs to be tested (Doolittle 1981;Simmons 2000;Galperin and Koonin 2012). Indeed, molecular biologists frequently list structural and functional homology as the most important alternative criteria to evolutionary homology when discussing sequence alignment, particularly for amino acid sequences.…”