Taxonomic distribution of proteins containing MR_MLE domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MR_MLE domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

On the origin of enzymatic species.

Petsko GA, Kenyon GL, Gerlt JA, Ringe D, Kozarich JW
Trends Biochem Sci. 1993; 18: 372-6

The diversity of enzyme catalytic function is remarkable, particularlywhen one considers that ancestral life forms must have started with a muchsmaller ensemble of proteins. In this article, we discuss the evolution ofthe mandelate pathway in pseudomonads as an example of how catalyticdiversity may have evolved. We suggest that existing enzymes that catalysethe chemistry needed to accomplish a transformation were recruited,followed by the evolution of specific binding.

Mandelate racemase and muconate lactonizing enzyme are mechanisticallydistinct and structurally homologous.

Neidhart DJ, Kenyon GL, Gerlt JA, Petsko GA
Nature. 1990; 347: 692-4

Mandelate racemase (MR) and muconate lactonizing enzyme (MLE) catalyseseparate and mechanistically distinct reactions necessary for thecatabolism of aromatic acids by Pseudomonas putida. The X-ray crystalstructure of MR, solved at 2.5 A resolution, reveals that the secondary,tertiary and quaternary structures of MR and MLE are remarkably similar;also, MR and MLE are about 26% identical in primary structure. However, MRhas no detectable MLE activity and vice versa. Thus, MR and MLE constitutethe first example of enzymes that catalyse different reactions, as opposedto mechanistically identical reactions on different substrates, yetpossess sufficient structural and sequence identity that they are likelyto have evolved from a common ancestor. The discovery that MR and MLEcatalyse different reactions but share a common structural framework hasbroad implications for the natural evolution of enzymes and metabolicpathways, as well as for the rational modification of enzyme activities.

Crystal structure of muconate lactonizing enzyme at 3 A resolution.

Goldman A, Ollis DL, Steitz TA
J Mol Biol. 1987; 194: 143-53

The crystal structure of muconate lactonizing enzyme has been solved at 3A resolution, and an unambiguous alpha-carbon backbone chain trace made.The enzyme contains three domains; the central domain is aparallel-stranded alpha-beta barrel, which has previously been reported insix other enzymes, including triose phosphate isomerase and pyruvatekinase. One novel feature of this enzyme is that its alpha-beta barrel hasonly seven parallel alpha-helices around the central core of eightparallel beta-strands; all other known alpha-beta barrels contain eightsuch helices. The N-terminal (alpha + beta) and C-terminal domains coverthe cleft where the eighth helix would be. The active site of muconatelactonizing enzyme has been found by locating the manganese ion that isessential for catalytic activity, and by binding and locating aninhibitor, alpha-ketoglutarate. The active site lies in a cleft betweenthe N-terminal and barrel domains; when the active sites of muconatelactonizing enzyme and triose phosphate isomerase are superimposed,barrel-strand 1 of triose phosphate isomerase is aligned withbarrel-strand 3 of muconate lactonizing enzyme. This implies thatstructurally homologous active-site residues in the two enzymes arecarried on different parts of the primary sequence; the ancestral genewould had to have been transposed during its evolution to the modernproteins, which seems unlikely. Therefore, these two enzymes may berelated by convergent, rather than divergent, evolution.