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Review
. 2023 Feb:72:102246.
doi: 10.1016/j.cbpa.2022.102246. Epub 2023 Jan 2.

Expanding the viewpoint: Leveraging sequence information in enzymology

Hayley L Knox  1 , Karen N Allen  2
Affiliations
Review

Expanding the viewpoint: Leveraging sequence information in enzymology

Hayley L Knox et al. Curr Opin Chem Biol. 2023 Feb.

Abstract

The use of protein sequence to inform enzymology in terms of structure, mechanism, and function has burgeoned over the past two decades. Referred to as genomic enzymology, the utilization of bioinformatic tools such as sequence similarity networks and phylogenetic analyses has allowed the identification of new substrates and metabolites, novel pathways, and unexpected reaction mechanisms. The holistic examination of superfamilies can yield insight into the origins and paths of evolution of enzymes and the range of their substrates and mechanisms. Herein, we highlight advances in the use of genomic enzymology to address problems which the in-depth analyses of a single enzyme alone could not enable.

Keywords: Enzyme evolution; Genome neighborhood; Genomic enzymology; Metabolic pathways; Sequence similarity network.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Overview of applications of genomic enzymology in recent years: determining pathways (PDB ID: 6P78), defining a superfamily or family (SSN generated from sequences from Knox et al. and visualized in Cytoscape [4]), exploring substrate specificity (PDB ID: 5V1V), understanding enzyme evolution, and predicting mechanism (mechanism adapted from Braffman et al. [5])
Figure 2.
Figure 2.
Abbreviated SSN of the FAO superfamily adapted from Tararina and Allen [16] and visualized in Cytoscape. The eight enzyme functional subgroups are labeled with representative structures for illustrative purposes. PDB IDs are 2IID (L-amino acid oxidase), 3NKS (protoporphyrinogen IX oxidase), 5KRQ (renalase), 6C71 (nicotine oxidoreductase), 1OJ9 (monoamine oxidase), 2UXN (lysine-specific demethylase), 5MOG (phytoene desaturase), and 5MBX (N1-acetylpolyamine oxidase).
Figure 3.
Figure 3.
An example of linker proteins found within a SSN, shown as purple boxes. The enzymes act as a “link” between the two clusters, illustrated in blue and red. SSN generated from sequences in O’Toole et al. [41] and visualized in Cytoscape.
Figure 4.
Figure 4.
Schematic example of RiPP processing. Amino acids and modified residues are represented by colored spheres.
See this image and copyright information in PMC

References

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