Evolution lactate dehydrogenase

G Wu, A Eiser, B ter Kuile, A Sail, M Muller. Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase. Proc Natl Acad Sci USA 96 6285-6290, 1999. 

Directed evolution of enzymes has been used to improve the reducing function of the enzymes. For example, this method was used to eliminate the cofactor requirement of B. stearothermophillus lactate dehydrogenase, which is activated in the presence of fructose 1,6-bisphosphate [12]. The activator is expensive and representative of the sort of cofactor complications that are undesirable in industrial processes. Three rounds of random mutagenesis and screening produced a mutant that is almost fully... 

Madern D, Cai X, Abrahamsen MS, Zhu G (2004) Evolution of Cryptosporidium parvum lactate dehydrogenase from malate dehydrogenase by a very recent event of gene duplication. Mol Biol Evol 21 489-497... 

Holland, L.Z., M. McFall-Ngai, and G.N. Somero (1997). Evolution of lactate dehydrogenase-A homologs of barracuda fishes (genus Sphyraena) from different thermal environments Differences in kinetic properties and thermal stability are due to amino acid substitutions outside the active site. Biochemistry 36 3207-3215. 

Figure 10.27. Isozymes of Lactate Dehydrogenase. (A) The rat heart LDH isozyme profile changes in the course of development. The H isozyme is represented by squares and the M isozyme by circles. The negative and positive numbers denote the days before and after birth, respectively. (B) LDH isozyme content varies by tissue. [(A) After W.-H. Li, Molecular Evolution (Sinauer, 1997), p. 283 (B) After K. Urich, Comparative Animal Biochemistry (S nngQrVQrlag, 1990), p. 542.]...

A fold also can be formed by one domain. In the example of secondary structures provided by lactate dehydrogenase (see Fig. 7.8), domain 1 alone forms the nucleotide binding fold. This fold is a binding site for NAD or, in other proteins, molecules with a generally similar structure (e.g., riboflavin). However, many proteins that bind NAD or NADP contain a very different fold from a separate fold family. These two different NAD binding folds arise from different ancestral lines and have different structures, but have similar properties and function. They are believed to be the product of convergent evolution. 

EVOLUTION OF PROTEIN STRUCTURE AND FUNCTION 705 (a) Lactate dehydrogenase (ILDN.pdb), domain 1 NAOH peroxidase (lNPX.pdb), domain 4... 

The second class of proteins in the aZ/S family of folds contains a large open sheet formed from mostly parallel /3-strands with helices on both sides. In contrast to the TIM barrel there are fewer limitations on the number of strands within the sheet and may vary from 4 to 10. The first example of this type of fold was seen in lactate dehydrogenase which contains a motif that is widely observed in dinucleotide binding proteins (this motif is often referred to as the Rossmann fold) and was the first example of a domain superfamily (Fig. 14b). The observation of a common fold in the dehydrogenases by Rossmann and coworkers started the entire field of structural comparison and study of structural evolution. 

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