The crystal structure of d- lactate dehydrogenase, a peripheral membrane respiratory enzyme

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Abstract
D -Lactate dehydrogenase ( d -LDH) of Escherichia coli is a peripheral membrane respiratory enzyme involved in electron transfer, located on the cytoplasmic side of the inner membrane. d -LDH catalyzes the oxidation of d -lactate to pyruvate, which is coupled to transmembrane transport of amino acids and sugars. Here we describe the crystal structure at 1.9 Å resolution of the three domains of d -LDH: the flavin adenine dinucleotide (FAD)-binding domain, the cap domain, and the membrane-binding domain. The FAD-binding domain contains the site of d -lactate reduction by a noncovalently bound FAD cofactor and has an overall fold similar to other members of a recently discovered FAD-containing family of proteins. This structural similarity extends to the cap domain as well. The most prominent difference between d -LDH and the other members of the FAD-containing family is the membrane-binding domain, which is either absent in some of these proteins or differs significantly. The d -LDH membrane-binding domain presents an electropositive surface with six Arg and five Lys residues, which presumably interacts with the negatively charged phospholipid head groups of the membrane. Thus, d -LDH appears to bind the membrane through electrostatic rather than hydrophobic forces.