Structural and functional similarities within the coenzyme binding domains of dehydrogenases

Ohlsson, Ingrid; Nordström, B.; Brändén, Carl‐Ivar

doi:10.1016/0022-2836(74)90523-3

Cited by 161 publications

(48 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is an Arg residue in NADP'dependent enzymes at the position equivalent to the Asp in both Drosophila and horse liver ADH. A sitedirected-mutagenesis study showed that changing this Arg residue to Met could alter cofactor specificity for NADPdependent glutathione reductase (Scrutton et al, 1990), supporting the hypothesis that the Asp residue in ADH could play an important role in cofactor specificity, as suggested by Ohlsson et al (1974). In order to determine the exact function of Asp38 in Drosophila ADH, mutants in which Asp38 has been replaced by Leu (D38L), Asn (D38N) and Arg (D38R) by site-directed mutagenesis have been constructed.…”

mentioning

confidence: 53%

Role of aspartic acid 38 in the cofactor specificity of Drosophila alcohol dehydrogenase

Chen

Lee

Chang

1991

European Journal of Biochemistry

View full text Add to dashboard Cite

Drosophila alcohol dehydrogenase (ADH), an NAD+‐dependent dehydrogenase, shares little sequence similarity with horse liver ADH. However, these two enzymes do have substantial similarity in their secondary structure at the NAD+‐binding domain [Benyajati, C., Place, A. P., Powers, D. A. & Sofer, W. (1981) Proc. Natl Acad. Sci. USA 78, 2717–2721]. Asp38, a conserved residue between Drosophila and horse liver ADH, appears to interact with the hydroxyl groups of the ribose moiety in the AMP portion of NAD+. A secondary‐structure enzymes also suggests that Asp38 could play an important role in cofactor specificity. Mutating Asp38 of Drosophila ADH into Asn38 decreases Km(app)NADP 62‐fold and increases kcat/Km(app)NADP 590‐fold at pH 9.8, when compared with wild‐type ADH. These results suggest that Asp38 is in the NAD+‐binding domain and its substituent, Asn38, allows Drosophila ADH to use both NAD+ and NADP+ as its cofactor. The observations from the experiments of thermal denaturation and kinetic measurement with pH also confirm that the repulsion between the negative charges of Asp38 and 2′‐phosphate of NADP+ is the major energy barrier for NADP+ to serve as a cofactor for Drosophila ADH.

show abstract

mentioning

confidence: 53%

Role of aspartic acid 38 in the cofactor specificity of Drosophila alcohol dehydrogenase

Chen

Lee

Chang

1991

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Although the resolution is too low to permit detailed interpretation these similarities strongly indicate an anti conformation for adenine around the glycosidic bond and the presence of a hydrogen bond between 0-2' of the ribose and the side-chain of Asp-223 [13].…”

Section: Resultsmentioning

confidence: 99%

The Crystal Structure of Complexes between Horse Liver Alcohol Dehydrogenase and the Coenzyme Analogues 3‐Iodopyridine‐adenine Dinucleotide and Pyridine‐adenine Dinucleotide

Samama

Zeppezauer

Biellmann

et al. 1977

European Journal of Biochemistry

View full text Add to dashboard Cite

We have studied the binding of the enzymatically active NAD + analogue, 3-iodopyridine-adenine dinucleotide, and the inactive analogue, pyridine-adenine dinucleotide to the enzyme horse liver alcohol dehydrogenase using X-ray crystallographic methods. These studies were made under such conditions that crystals of the complexes were isomorphous to apocnzyme crystals. Both analogues bind in the same conformation. The binding of the adenosine moiety is very similar to that of ADP-ribose or NADH bound to the enzyme. The conformation and mode of binding of the remaining portions of the analogue molecules is, however, quite different. The pyridine ring is not situated in the active-site pocket as the nicotinamide group in thc isomorphous enzyme -NADH . imidazole complex but lies at the surface of the crevice between the two domains of the subunit, approximately 1.5 nm away from the catalytically active zinc atom. Lys-228 which has been shown to be important for NADH dissociation is in this region of the molecule.A large number of analogues to the coenzyme NAD' have been investigated [l] in order to delineate the role of the various moieties of the dinucleotide in the interaction of this coenzyme with the NAD+-dependent dehydrogenases. We have been particularly interested in the enzymatic effects of substitutions on the nicotinamide ring. As part of these studies, and also for thc use as heavy-atom derivatives in protein Crystallography, we synthesized 3-iOdO and subsequently 3-bromo and 3-chloro derivatives of pyridineadenine dinucleotide which were active in enzymatic hydrogen transfer reactions. Synthesis of these analogues and their kinetic properties for some NAD+-dependent dehydrogenase-catalysed reactions is presented elsewhere [2].The present study describes the binding of the 3-iodo analogue to one of these enzymes, horse liver alcohol dehydrogenase, as studied by X-ray crystallographic methods. Furthermore, the results of that Abbreviations.Pd AD + . pyridine-adenine dinucleot ide ; io3PdAD+, 3-iodopyridine-adenine dinucleotide; Tes, 2-([tris-(hydroxymethyl)methyi]amino)ethane sulfonic acid.

show abstract

“…6), allowing 150 -200 bp for the poly(A) tail. The N terminus of the protein has sequence homology to an ADP-␤␣␤-binding fold, typical for proteins that bind FAD, NAD ϩ , or NADP ϩ (45,46). The last three amino acids, AHL, represent a peroxisomal targeting signal 1 (PTS1), characteristic for mammalian proteins that are translocated into peroxisomes (47).…”

Section: Purification Of Sarcosinementioning

confidence: 99%

Cloning and Functional Expression of a Mammalian Gene for a Peroxisomal Sarcosine Oxidase

Reuber

Karl

Reimann

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Sarcosine oxidation in mammals occurs via a mitochondrial dehydrogenase closely linked to the electron transport chain. An additional H 2 O 2 -producing sarcosine oxidase has now been purified from rabbit kidney. A corresponding cDNA was cloned from rabbit liver and the gene designated sox. This rabbit sox gene encodes a protein of 390 amino acids and a molecular mass of 44 kDa identical to the molecular mass estimated for the purified enzyme. Sequence analysis revealed an N-terminal ADP-␤␣␤-binding fold, a motif highly conserved in tightly bound flavoproteins, and a C-terminal peroxisomal targeting signal 1. Sarcosine oxidase from rabbit liver exhibits high sequence homology (25-28% identity) to monomeric bacterial sarcosine oxidases. Both purified sarcosine oxidase and a recombinant fusion protein synthesized in Escherichia coli contain a covalently bound flavin, metabolize sarcosine, L-pipecolic acid, and L-proline, and cross-react with antibodies raised against L-pipecolic acid oxidase from monkey liver. Subcellular fractionation demonstrated that sarcosine oxidase is a peroxisomal enzyme in rabbit kidney. Transfection of human fibroblast cell lines and CV-1 cells (monkey kidney epithelial cells) with the sox cDNA resulted in a peroxisomal localization of sarcosine oxidase and revealed that the import into the peroxisomes is mediated by the peroxisomal targeting signal 1 pathway.In mammals a variety of H 2 O 2 -producing oxidases including D-amino-acid oxidase, D-aspartate oxidase, L-hydroxy-acid oxidase, acyl-CoA oxidase, and L-pipecolic acid oxidase are compartmentalized in peroxisomes. The H 2 O 2 generated from these reactions is then converted to H 2 O and O 2 by the peroxisomal matrix enzyme catalase (1). Several disorders have been described in which there is a defect in peroxisomal assembly that results in a partial or total absence of peroxisomal functions (for a review see Ref.2). Patients with these peroxisomal disorders such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and hyperpipecolatemia all have elevated levels of L-pipecolic acid, an imino acid, which in human and monkey liver is oxidized by a peroxisomal L-pipecolic acid oxidase (3). Indeed, L-pipecolic acid oxidase activity was not detected in liver samples from patients with Zellweger syndrome (4). Primates dehydrogenate L-pipecolic acid to ␦-piperideine-6-carboxylate which is spontaneously converted to ␣-aminoadipic acid ␥-semialdehyde.The subcellular localization of this pathway seems to differ in other mammalian species. In rabbits, guinea pigs, dogs, and sheep L-pipecolic acid oxidation is primarily mitochondrial (5). However, during our studies examining the subcellular distribution of L-pipecolic acid oxidation in rabbits, a considerable amount of L-pipecolic acid oxidation was detected in the peroxisomes, in addition to the previously reported mitochondrial activity (6). Interestingly, this peroxisomal enzyme showed a high specific activity for sarcosine and also oxidized L-pipecolic acid and L-p...

show abstract

Structural and functional similarities within the coenzyme binding domains of dehydrogenases

Cited by 161 publications

References 21 publications

Role of aspartic acid 38 in the cofactor specificity of Drosophila alcohol dehydrogenase

Role of aspartic acid 38 in the cofactor specificity of Drosophila alcohol dehydrogenase

The Crystal Structure of Complexes between Horse Liver Alcohol Dehydrogenase and the Coenzyme Analogues 3‐Iodopyridine‐adenine Dinucleotide and Pyridine‐adenine Dinucleotide

Cloning and Functional Expression of a Mammalian Gene for a Peroxisomal Sarcosine Oxidase

Contact Info

Product

Resources

About