Stereochemistry and accessibility of prosthetic groups in flavoproteins.
Using 8-demethyl-8-hydroxy-5-deaza-5-carba analogues of the appropriate flavin nucleotides, we determined the stereochemistry of interaction between coenzyme and substrate for several flavoproteins. The enzymes were D-amino acid oxidase, L-lactate oxidase, and D-lactate dehydrogenase, all three of which interact with pyruvate, as well as cyclohexanone monooxygenase and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase, which were both probed with nicotinamide nucleotides. L-Lactate oxidase and D-lactate dehydrogenase used the si face of the modified flavin ring while the other three enzymes showed re-side specificity. This selection of flavoenzymes includes FAD- and FMN-dependent enzymes, enzymes that follow a carbanion mechanism, and others that have hydride transfer as an integral part of their reaction pathway.
D001051:Apoenzymes / Q000378:metabolism*; D001059:Apoproteins / Q000378:metabolism*; D003605:D-Amino-Acid Oxidase / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005415:Flavins / Q000378:metabolism*; D005420:Flavoproteins / Q000378:metabolism*; D005949:Glucose Oxidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D013237:Stereoisomerism
D001051:Apoenzymes; D001059:Apoproteins; D005415:Flavins; D005420:Flavoproteins; D005182:Flavin-Adenine Dinucleotide; D005486:Flavin Mononucleotide; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D007770:L-Lactate Dehydrogenase; D005949:Glucose Oxidase; C021497:lactate 2-monooxygenase; C019483:methylhydroxypyridine-carboxylate dioxygenase; D044943:Fatty Acid Desaturases; D003605:D-Amino-Acid Oxidase