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The B6 database: a tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families.

Percudani R, Peracchi A - BMC Bioinformatics (2009)

Bottom Line: An example of such analyses (a census of human genes coding for PLP-dependent enzymes) is provided here, whereas many more are accessible through the database itself.The B6 database is a curated repository of biochemical and molecular information about an important group of enzymes.This information is logically organized and available for computational analyses, providing a key resource for the identification, classification and comparative analysis of B6-dependent enzymes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Parma, 43100 Parma, Italy. riccardo.percudani@unipr.it

ABSTRACT

Background: Enzymes that depend on vitamin B6 (and in particular on its metabolically active form, pyridoxal 5'-phosphate, PLP) are of great relevance to biology and medicine, as they catalyze a wide variety of biochemical reactions mainly involving amino acid substrates. Although PLP-dependent enzymes belong to a small number of independent evolutionary lineages, they encompass more than 160 distinct catalytic functions, thus representing a striking example of divergent evolution. The importance and remarkable versatility of these enzymes, as well as the difficulties in their functional classification, create a need for an integrated source of information about them.

Description: The B6 database http://bioinformatics.unipr.it/B6db contains documented B6-dependent activities and the relevant protein families, defined as monophyletic groups of sequences possessing the same enzymatic function. One or more families were associated to each of 121 PLP-dependent activities with known sequences. Hidden Markov models (HMMs) were built from family alignments and incorporated in the database. These HMMs can be used for the functional classification of PLP-dependent enzymes in genomic sets of predicted protein sequences. An example of such analyses (a census of human genes coding for PLP-dependent enzymes) is provided here, whereas many more are accessible through the database itself.

Conclusion: The B6 database is a curated repository of biochemical and molecular information about an important group of enzymes. This information is logically organized and available for computational analyses, providing a key resource for the identification, classification and comparative analysis of B6-dependent enzymes.

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Homology network of PLP-dependent enzymes. Nodes represent Hidden Markov models (HMMs) of PLP-dependent families. Edges represent homology connections (E < 10-5) between families established by HMM-HMM comparisons [18]. Black edges connect protein families with the most significant similarities (E < 10-50). The network is visualized with the "Degree sorted circle layout" of Cytoscape [19]. Colors were mapped into nodes using the structural group of the protein family as a node property.
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Figure 3: Homology network of PLP-dependent enzymes. Nodes represent Hidden Markov models (HMMs) of PLP-dependent families. Edges represent homology connections (E < 10-5) between families established by HMM-HMM comparisons [18]. Black edges connect protein families with the most significant similarities (E < 10-50). The network is visualized with the "Degree sorted circle layout" of Cytoscape [19]. Colors were mapped into nodes using the structural group of the protein family as a node property.

Mentions: To elucidate the relationships between the 149 enzyme families defined as above, we performed an all versus all comparison of the families in the database using an HMM-HMM alignment software [18]. The results of this comparison were analyzed with an interaction network software [19] to build an homology-based network of PLP-dependent families (Figure 3). By considering only significant similarities (E < 10-5) between HMMs, the analysis identified seven separated clusters of PLP-dependent families (Figure 3). Five of these clusters corresponded to the traditional classification of PLP-dependent enzymes into five distinct structural groups (fold types I to V). Of the two additional clusters, one included lysine 5,6-aminomutase (EC: 5.4.3.4) and the other lysine 2,3-aminomutase (EC: 5.4.3.2) - two enzymes whose structures have been recently determined and found to be different from the known structures of PLP-dependent enzymes [20,21]. In the database, the protein families belonging to these two clusters were assigned, respectively, to fold types VI and VII.


The B6 database: a tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families.

Percudani R, Peracchi A - BMC Bioinformatics (2009)

Homology network of PLP-dependent enzymes. Nodes represent Hidden Markov models (HMMs) of PLP-dependent families. Edges represent homology connections (E < 10-5) between families established by HMM-HMM comparisons [18]. Black edges connect protein families with the most significant similarities (E < 10-50). The network is visualized with the "Degree sorted circle layout" of Cytoscape [19]. Colors were mapped into nodes using the structural group of the protein family as a node property.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2748086&req=5

Figure 3: Homology network of PLP-dependent enzymes. Nodes represent Hidden Markov models (HMMs) of PLP-dependent families. Edges represent homology connections (E < 10-5) between families established by HMM-HMM comparisons [18]. Black edges connect protein families with the most significant similarities (E < 10-50). The network is visualized with the "Degree sorted circle layout" of Cytoscape [19]. Colors were mapped into nodes using the structural group of the protein family as a node property.
Mentions: To elucidate the relationships between the 149 enzyme families defined as above, we performed an all versus all comparison of the families in the database using an HMM-HMM alignment software [18]. The results of this comparison were analyzed with an interaction network software [19] to build an homology-based network of PLP-dependent families (Figure 3). By considering only significant similarities (E < 10-5) between HMMs, the analysis identified seven separated clusters of PLP-dependent families (Figure 3). Five of these clusters corresponded to the traditional classification of PLP-dependent enzymes into five distinct structural groups (fold types I to V). Of the two additional clusters, one included lysine 5,6-aminomutase (EC: 5.4.3.4) and the other lysine 2,3-aminomutase (EC: 5.4.3.2) - two enzymes whose structures have been recently determined and found to be different from the known structures of PLP-dependent enzymes [20,21]. In the database, the protein families belonging to these two clusters were assigned, respectively, to fold types VI and VII.

Bottom Line: An example of such analyses (a census of human genes coding for PLP-dependent enzymes) is provided here, whereas many more are accessible through the database itself.The B6 database is a curated repository of biochemical and molecular information about an important group of enzymes.This information is logically organized and available for computational analyses, providing a key resource for the identification, classification and comparative analysis of B6-dependent enzymes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Parma, 43100 Parma, Italy. riccardo.percudani@unipr.it

ABSTRACT

Background: Enzymes that depend on vitamin B6 (and in particular on its metabolically active form, pyridoxal 5'-phosphate, PLP) are of great relevance to biology and medicine, as they catalyze a wide variety of biochemical reactions mainly involving amino acid substrates. Although PLP-dependent enzymes belong to a small number of independent evolutionary lineages, they encompass more than 160 distinct catalytic functions, thus representing a striking example of divergent evolution. The importance and remarkable versatility of these enzymes, as well as the difficulties in their functional classification, create a need for an integrated source of information about them.

Description: The B6 database http://bioinformatics.unipr.it/B6db contains documented B6-dependent activities and the relevant protein families, defined as monophyletic groups of sequences possessing the same enzymatic function. One or more families were associated to each of 121 PLP-dependent activities with known sequences. Hidden Markov models (HMMs) were built from family alignments and incorporated in the database. These HMMs can be used for the functional classification of PLP-dependent enzymes in genomic sets of predicted protein sequences. An example of such analyses (a census of human genes coding for PLP-dependent enzymes) is provided here, whereas many more are accessible through the database itself.

Conclusion: The B6 database is a curated repository of biochemical and molecular information about an important group of enzymes. This information is logically organized and available for computational analyses, providing a key resource for the identification, classification and comparative analysis of B6-dependent enzymes.

Show MeSH