Knowledge-based modeling of the D-lactate dehydrogenase three-dimensional structure.
A three-dimensional structure of the NAD-dependent D-lactate dehydrogenase of Lactobacillus bulgaricus is modeled using the structure of the formate dehydrogenase of Pseudomonas sp. as template. Both sequences share only 22% of identical residues. Regions for knowledge-based modeling are defined from the structurally conserved regions predicted by multiple alignment of a set of related protein sequences with low homology. The model of the D-LDH subunit shows, as for the formate dehydrogenase, an alpha/beta structure, with a catalytic domain and a coenzyme binding domain. It points out the catalytic histidine (His-296) and supports the hypothetical catalytic mechanism. It also suggests that the other residues involved in the active site are Arg-235, possibly involved in the binding of the carboxyl group of the pyruvate, and Phe-299, a candidate for stabilizing the methyl group of the substrate.
Vinals
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C
Facultés Universitaires Notre Dame de la Paix, Namur, Belgium.
De Bolle
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X
Depiereux
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Feytmans
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E
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004284:Dogfish; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D007778:Lactobacillus / Q000737:chemistry / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009243:NAD / Q000378:metabolism; D011487:Protein Conformation; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid
D011773:Pyruvates; D009243:NAD; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase