Stereochemistry and accessibility of prosthetic groups in flavoproteins

• Published in: Biochemistry (Easton) Vol. 27; no. 7; pp. 2300 - 2305
• Main Authors: Manstein, Dietmar J, Massey, Vincent, Ghisla, Sandro, Pai, Emil F
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 05.04.1988
• Subjects: analogs; Apoenzymes - metabolism; Apoproteins - metabolism; Biological and medical sciences; D-Amino-Acid Oxidase - metabolism; Fatty Acid Desaturases - metabolism; Flavin Mononucleotide - metabolism; Flavin-Adenine Dinucleotide - metabolism; Flavins - metabolism; Flavoproteins - metabolism; flavor; Fundamental and applied biological sciences. Psychology; Glucose Oxidase - metabolism; Interactions. Associations; Intermolecular phenomena; L-Lactate Dehydrogenase - metabolism; Mixed Function Oxygenases - metabolism; Molecular biophysics; Oxidoreductases - metabolism; prosthetic groups; Stereoisomerism; Flavin enzyme; FMN; Active site; FAD; D-Amino-acid oxidase; Molecular interaction; Flavoprotein; Stereochemistry; Coenzyme; Substrate; Flavin; Molecular orientation; D»-Lactate dehydrogenase; Molecular accessibility
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00407a009

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.