Abstract
Leucine decarboxylase (LDC) is a recently proposed enzyme with no official enzyme commission number yet. It is encoded by the Mus musculus gene Gm853 which is expressed at kidneys, generating isopentylamine, an alkylmonoamine that has not been described to be formed by any metazoan enzyme yet. Although the relevance of LDC in mammalian physiology has not been fully determined, isopentylamine is a potential modulator which may have effects on insulin secretion and healthy gut microbiota formation. The LDC is a stable enzyme that specifically decarboxylates L-leucine but does not decarboxylate ornithine or lysine as its paralogues ornithine decarboxylase (ODC; EC: 4.1.1.17) and lysine decarboxylase (KDC; EC: 4.1.1.18) do. It does not act as an antizyme inhibitor and does not decarboxylate branched amino acids such as valine and isoleucine as it is another paralogue valine decarboxylase (VDC; EC: 4.1.1.14). The crystal structure of the enzyme has not been determined yet but there are homologous structures with complete coverage in Protein Data Bank (PDB) which makes LDC a good candidate for comparative modelling.In this study, homology models of LDC were generated and used in cofactor and substrate docking to understand the structure/function relationship underlying the unique selectivity of LDC enzyme.
Highlights
Polyamines are biologically important poly-cations that are essential for many important biological processes including protein and nucleic acid synthesis, native structure formation, protection from oxidative damage, block and modulation of ion channels, cell proliferation, cell differentiation, and apoptosis [1]
Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first enzyme in the polyamine synthesis [2] and is a member of group IV amino acid decarboxylases which is a subset of pyridoxal-5’-phosphate (PLP)-dependent enzymes that participate in the generation of biogenic amines or neurotransmitters [3]
This reaction is the committed step in polyamine synthesis
Summary
Polyamines are biologically important poly-cations that are essential for many important biological processes including protein and nucleic acid synthesis, native structure formation, protection from oxidative damage, block and modulation of ion channels, cell proliferation, cell differentiation, and apoptosis [1]. Due to their crucial function in the cell, polyamine levels are strictly controlled through various mechanisms. LDC acts on leucine but not ornithine, lysine (Lys, K) valine (Val, V), or isoleucine (Ile, I) and does not act as an antizyme inhibitor. Comparative models of LDC is generated and used to investigate the cofactor and substrate interaction for gaining a better understanding on the structure/function relationship and unique substrate selectivity of the novel enzyme
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