Common structural elements in the architecture of the cofactor-binding domains in unrelated families of pyridoxal phosphate-dependent enzymes

Abstract

A detailed comparison of the structures of aspartate aminotransferase, alanine race-mase, the beta subunit of tryptophan synthase, D-amino acid aminotransferase and glycogen phosphorylase has revealed more extensive structural similarities among pyridoxal phosphate (PLP)-binding domains in these enzymes than was observed previously. These similarities consist of seven common structural segments of the polypeptide chain, which form an extensive common structural organization of the backbone chain responsible for the appropriate disposition of key residues, some from the aligned fragments and some from variable loops joined to these fragments, interacting with PLPs in these enzymes. This common structural organization contains an analogous hydrophobic minicore formed from four amino acid side chains present in the two most conserved structural elements. In addition, equivalent alpha-beta-alpha-beta supersecondary structures are formed by these seven fragments in three of the five structures: alanine racemase, tryptophan synthase and glycogen phosphorylase. Despite these similarities, it is generally accepted that these proteins do not share a common heritage, but have arisen on five separate occasions. The common and contiguous alpha-beta-alpha-beta structure accounts for only 28 residues and all five enzymes differ greatly in both the orientation of the PLP pyridoxal rings and their contacts with residues close to the common structural elements.

Divergence and Convergence in Enzyme Evolution

“…A subsequent comparison of the adenine-binding sites revealed a common structural framework with similar polar and hydrophobic interactions in representatives of eight different folds (74). A similar pattern of structural convergence of evolutionarily unrelated enzymes has been revealed in the organization of pyridoxal phosphate-interacting residues of pyridoxal phosphate-dependent enzymes representing five distinct folds (75). Similar examples of functional convergence can be seen in NISEs, which, by definition, act on the same substrates.…”

Genetic and Structural Organization of the Aminophenol Catabolic Operon and Its Implication for Evolutionary Process

“…Both of these enzymes have hexameric structures and share tautomerization reactions in catalysis (21). Analyzing the amino acid sequence of NbzE, we could not find any similarity with other deaminases reported so far, and NbzE seems not to possess any cofactor binding site commonly found in several types of deamination-catalyzing enzymes, such as PLP in aminotransferase (12), NAD ϩ in glutamate dehydrogenase (51), and a Zn ϩ coordinate site in adenosine deaminases (3). Instead, we observed a modest level of amino acid identity between part of NbzE and XylH, and the nbzE gene has identity as high as 54% with the xylH gene, which implies a close evolutionary relationship between these genes.…”

Live-cell high resolution magic angle spinning magnetic resonance spectroscopy for in vivo analysis of Pseudomonas aeruginosa metabolomics

“…As we also detected signals diagnostic of lipopolysaccharides (LPS), we deduce that the PA cell wall contains LPS. In addition, the 3.56 ppm peak signal, likely corresponding to glycine, is highly suggestive of cell-wall peptidoglycans and purine biosynthesis, particularly since the 3.56 ppm peak is from [ 1 -H] glycine metabolism in purine biosynthesis (30). Alanine, which is important in peptidoglycan biosynthesis and signaling pathways, was also detected.…”