Dehydrogenases known structures

NADH cytochrome c reductase was isolated from pigeon breast and pig heart muscle. The enzyme was shown to contain four atoms of iron per flavin molecule. NADH cytochrome c reductase, like succinic dehydrogenase, is a ferroflavoprotein. The ratio of iron to flavin is four. The enzyme contains sulfhydryl groups that can be titrated by classical methods, but their oxidation has no effect on the enzymatic activity. In contrast, the removal of the metal leads to a decrease in the ability of the enzyme to reduce cytochrome c. As for succinic dehydrogenase, the structure of the flavin in NADH cytochrome c reductase is not clear. It was demonstrated that it is not flavin mononucleotide, but the identity of the flavin component with flavin adenine dinucleotide is not established in fact, the flavin component differs from the classical FAD by its chromatographic properties and its behavior in enzymic assays. It is not known if it is a structural variation of the flavin nucleotide or if the nucleotide is conjugated to a peptide. 

The three known crystal structures of molybdopterin-containing enzymes are from members of the first two families the aldehyde oxido-reductase from D. gigas (MOP) belongs to the xanthine oxidase family (199, 200), whereas the DMSO reductases from Rhodobacter (R.) cap-sulatus (201) and from/ , sphaeroides (202) and the formate dehydrogenase from E. coli (203) are all members of the second family of enzymes. There is a preliminary report of the X-ray structure for enzymes of the sulfite oxidase family (204). 

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

In addition to these more-or-less well characterized proteins, iron is known to be bound to certain flavoproteins such as succinic dehydrogenase (20), aldehyde oxidase (27), xanthine oxidase (22) and dihydrooro-tate dehydrogenase (23). Iron is present and functional in non-heme segments of the electron transport chain but again no real structural information is at hand (24). 

Since the primary structure of a peptide determines the global fold of any protein, the amino acid sequence of a heme protein not only provides the ligands, but also establishes the heme environmental factors such as solvent and ion accessibility and local dielectric. The prevalent secondary structure element found in heme protein architectures is the a-helix however, it should be noted that p-sheet heme proteins are also known, such as the nitrophorin from Rhodnius prolixus (71) and flavocytochrome cellobiose dehydrogenase from Phanerochaete chrys-osporium (72). However, for the purpose of this review, we focus on the structures of cytochromes 6562 (73) and c (74) shown in Fig. 2, which are four-a-helix bundle protein architectures and lend themselves as resource structures for the development of de novo designs. 

Valproic acid and its salts are a new group of antiepileptic drugs that differs from the known drugs both structurally and in terms of its mechanism of action. It is believed that it acts on the metabolism of the GABA system. Valproic acid has been shown to elevate the level of GABA in the brain by means of competitive inhibition of GABA transaminase and the dehydrogenase of succinic semialdehyde. 

Although zinc itself is not redox-active, some class I enzymes containing zinc in their active sites are known. The most prominent are probably alcohol dehydrogenase and copper-zinc superoxide dismutase (Cu,Zn-SOD). AU have in common that the redox-active agent is another transition-metal ion (copper in Cu,Zn-SOD) or a cofactor such as nicotinamide adenine dinucleotide (NAD+/NADH). The Zn(II) ion affects the redox reaction only in an indirect manner, but is nevCTtheless essential and cannot be regarded simply as a structural factor. 

The flavoproteins known to contain covalently-found prosthetic groups are listed in Table 2. In addition to the flavoproteins also carcosine oxidase from Corynebacterium contains a covalently-bound FAD Its mode of linkage is not yet known. Furthermore it seems to be the first enzyme reported to contain equivalent amounts of covalently-bound and dissociable FAD. Djmehtlyglycine dehydrogenase prossesses also a covalently linked prosthetic group, which structure is probably identical with that of (2)... 

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