Figure 1.
The three-dimensional structure, functional contexts, and genomic contexts of FGGY kinases.
(A) The three-dimensional structure of a FGGY kinase (left) and a spectrum of substrates that may be utilized by this family (right). The FGGY_N and FGGY_C domains are colored red and green, respectively, shown in the example of a glycerol kinase (GlpK) from E. coli (PDB 1GLA). The co-product ADP was projected into the binding site from the structure of another FGGY protein (PDB 2UYT). The substrates that are utilized by T. maritima were marked with a star (*) with corresponding colors to the pathways in Figure 1B. (B) Overview of the metabolic pathways that employ FGGY kinases, shown in the example of a hyperthermophilic bacterium, Thermotoga maritima. The enzyme names and their encoding genes in the T. maritima genome are shown using respective background colors (as the shade or the frame) that indicate individual pathways, where the shaded boxes indicate genes in the genomic context of FGGY genes (shown in Figure 1C). The five FGGY kinases encoded in the T. maritime genome and their respective substrates are highlighted using black frames. Abbreviations: GlpF—glycerol uptake facilitator protein; GlpK—glycerol kinase; GlpD—glycerol-3-phosphate dehydrogenase; AraNPQ—alpha-arabinosides ABC transport system; AbfA—alpha-N-arabinofuranosidase; AraA—L-arabinose isomerase; AraB—L-ribulokinase; AraD—L-ribulose-5-phosphate-4-epimerase; RhaFGHI—rhamnose oligosaccharide ABC transporter; RhaA—L-rhamnose isomerase; RhaB—rhamnulokinase; RhaD—rhamnulose-1-phosphate aldolase; XtpHJLMG—Xylan oligosaccharide ABC transporter; XloEFGKL—Xylose oligosaccharides ABC transporter; XylEFG—Xylose ABC transporter; XynB—Beta-xylosidase; XylQ—alpha-xylosidase; XylA—Xylose isomerase; XylB—xylulose kinase; IdnO—gluconate 5-dehydrogenase; GntK—gluconokinase; Gnd—6-phosphogluconate dehydrogenase; Rpe—ribulose-phosphate-3-epimerase. (C) The genomic context of FGGY kinases in T. maritima. Each arrow indicates a gene in the T. maritima genome, and their relative positions indicate the distance between different genes.
Table 1.
The list of nine functions observed for the proteins in the FGGY kinase family.
Figure 2.
Phylogenetic tree of proteins from the annotated protein set CARS (a subset of the entire FGGY kinase family).
The root was determined by using UvrC proteins (not shown) as an out-group, and the deep splits with a bootstrapping value higher than 40 are marked with numbers indicating their bootstrapping values. The branches are colored based on their functional specificities, and the color scheme is consistent with that used in Figure 1B. Some isofunctional groups were further divided into subgroups based on their positions in the tree, which is reflected in their labels. The amino acid distribution of specificity-determining positions (SDPs) are shown as logo characters produced by the Weblogo program [31]. The branches with three-dimensional structural information are marked with a star, and the branches supported by literature information are marked with a black dot. The numbers in the black dots indicate the different species from which FGGY proteins were identified: 1—Thermotoga maritima; 2—Escherichia coli; 3—Bacillus subtilis; 4—Brucella abortus; 5—Candida sp. Xu316; 6—Corynebacterium glutamicum; 7—Enterococcus faecalis; 8—Haemophilus influenzae; 9—Klebsiella pneumoniae; 10—Lactobacillus brevis; 11—Lactobacillus pentosus; 12—Pichia stipitis; 13—Salmonella typhimurium; 14—Streptococcus pneumoniae; 15—Streptomyces rubiginosus; 16—Thermus aquaticus; 17—Thermus thermophilus; 18—Trypanosoma brucei.
Figure 3.
Position of signature residues in the three-dimensional structures of FGGY kinases.
Labels in each cell show the protein and chain identification numbers from the Protein Data Bank [29], as well as the protein function. The protein backbone is shown in white cartoon representation, the signature residues are marked with red sticks, and the co-crystallized substrates are marked as cyan sticks.
Figure 4.
Protein similarity networks reconstructed based on entire sequences (A), as well as signature sequences (B), for all FGGY proteins in CARS.
Each node in the network represents a single protein in the annotated dataset, and each edge represents a BLAST alignment with an E-value better then a given threshold indicated in the graph. The nodes are colored according to their functions (see Legend—color scheme is the same as in Figure 2). The edges are colored in a gray scale: the darker the color is, the more significant the similarity is. The nodes were arranged using the yFiles organic layout provided with Cytoscape version 2.7 [47].
Figure 5.
Distribution of FGGY kinase functions in a species tree extracted from a published tree of bacterial species [32].
Branches in the species tree were collapsed to show the higher taxonomic level. The colored rectangle bars (color scheme is the same as in Figure 2) on the right shows the functional distributions of each taxonomic group. The width of the bar indicates the proportion of species within a taxonomic group containing a specific function. The XylB and AraB groups are numbered according to the divisions in the protein tree to show their evolutionary patterns. The original layout was made with the Web interface of iTol [49] and was proportionally scaled and manually labeled. All rectangle bars were zoomed in proportionally so that they could be highlighted in the graph.
Figure 6.
The proposed evolutionary model of the FGGY kinase family.