Aldehyde dehydrogenase homologous folate enzymes: evolutionary switch between cytoplasmic andmitochondrial localization. Chem Biol Interact. 2014 Dec 27, Krupenko NI1, Holmes RS2, Tsybovsky Y3, Krupenko SA4.
- Department of Nutrition, UNC-Chapel Hill, UNC Nutrition Research Institute, Kannapolis, NC 28081, United States.
- 2The Eskitis Institute for Drug Discovery and School of Natural Sciences, Griffith University, Nathan 4111 Brisbane, Queensland, Australia.
- 3Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, United States.
- 4Department of Nutrition, UNC-Chapel Hill, UNC Nutrition Research Institute, Kannapolis, NC 28081, United States. Electronic address: firstname.lastname@example.org.
Cytosolic and mitochondrial 10-formyltetrahydrofolate dehydrogenases are products of separate genes in vertebrates but only one such gene is present in invertebrates. There is a significant degree of sequence similarity between the two enzymes due to an apparent origin of the gene for themitochondrial enzyme (ALDH1L2) from the duplication of the gene for the cytosolic enzyme (ALDH1L1). The primordial ALDH1L gene originated from a natural fusion of three unrelated genes, one of which was an aldehyde dehydrogenase. Such structural organization defined the catalytic mechanism of these enzymes, which is similar to that of aldehyde dehydrogenases. Here we report the analysis of ALDH1L1 and ALDH1L2 genes from different species and their phylogeny and evolution. We also performed sequence and structure comparison of ALDH1L enzymes possessingaldehyde dehydrogenase catalysis to those lacking this feature in an attempt to explain mechanistic differences between cytoplasmic ALDH1L1 andmitochondrial ALDH1L2 enzymes and to better understand their functional roles.
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