A genomic overview of pyridoxal‐phosphate‐dependent enzymes

Abstract

Enzymes that use the cofactor pyridoxal phosphate (PLP) constitute a ubiquitous class of biocatalysts. Here, we analyse their variety and genomic distribution as an example of the current opportunities and challenges for the study of protein families. In many free-living prokaryotes, almost 1.5% of all genes code for PLP-dependent enzymes, but in higher eukaryotes the percentage is substantially lower, consistent with these catalysts being involved mainly in basic metabolism. Assigning the function of PLP-dependent enzymes simply on the basis of sequence criteria is not straightforward because, as a consequence of their common mechanistic features, these enzymes have intricate evolutionary relationships. Thus, many genes for PLP-dependent enzymes remain functionally unclassified, and several of them might encode undescribed catalytic activities. In addition, PLP-dependent enzymes often show catalytic promiscuity (that is, a single enzyme catalyses different reactions), implying that an organism can have more PLP-dependent activities than it has genes for PLP-dependent enzymes. This observation presumably applies to many other classes of protein-encoding genes.

Vitamin B-6 Metabolism and Interactions with TNAP

“…Pyridoxal phosphate is a cofactor for over 150 enzymes representing every major class of enzymes except ligases (http:// enzyme.expasy.org). This accounts for about 4 % of known enzyme activity (Percudani and Peracchi 2003). These enzymes catalyze reactions including transamination, decarboxylation, racemization, aldol cleavage, and beta and gamma eliminations and replacement reactions leading Jansonius (1998) to conclude that pyridoxal phosphate is the most versatile organic catalyst known.…”

Crystal Structure of Pyridoxal Biosynthesis Lyase PdxS from Pyrococcus horikoshii

“…Pyridoxal 5′-phosphate (PLP) is the biologically active form of vitamin B 6 and is essential for numerous enzyme reactions, including transamination, decarboxylation, racemization, and elimination in amino acid metabolism, biosynthesis of antibiotics, and DNA biosynthesis (Eliot and Kirsch, 2004;Percudani and Peracchi, 2003). As de novo PLP biosynthesis pathways exist in bacteria, fungi, protozoa, and plants, but are missing in mammals, PLP biosynthesis could be a target for developing antibiotics (Belitsky, 2004;Dong et al, 2004;Osmani et al, 1999).…”

Functional Diversity of Haloacid Dehalogenase Superfamily Phosphatases from Saccharomyces cerevisiae

“…This discrepancy once again demonstrates that at low sequence similarity (roughly less than 30% identity with HADs), homology-based prediction of enzyme substrate specificity (as opposed to the general type of the catalyzed reaction) often results in erroneous functional annotations. PLP is the active form of vitamin B 6 , which is an essential cofactor in all organisms involved in a broad variety of enzymatic reactions (110). The intracellular level of PLP is mainly controlled by its synthesis, binding to enzymes, and degradation by phosphatases (111,112).…”