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- Jornvall, H., et al.
(author)
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Multiplicity of eukaryotic ADH and other MDR forms
- 2003
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In: Chemico-Biological Interactions. - 0009-2797 .- 1872-7786. ; 143-144, s. 255-261
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Conference paper (other academic/artistic)abstract
- Eukaryotic genomes code for at least eight medium-chain dehydrogenases/reductases (MDR) enzyme families of two types, with and without Zn2+ at the active site. Four families have Zn2+: 'Dimeric alcohol dehydrogenases (ADHs)' (including liver ADHs), 'Tetrameric ADHs' (including the yeast ADHs), 'Cinnamyl ADHs' and 'Polyol DHs'. In the human genome, there are minimally 23 MDR genes, but the list is still growing from further interpretations. Of these, seven genes on chromosome 4 (and three pseudogenes) represent the ADH classes in the gene order IV, I?, Iß, Ia, V, II and III. The lineages leading to human ADH establish five levels of divergence, with nodes at the MDR/short-chain dehydrogenases/reductases (SDR), dimer/tetramer, class III/non-III, further class, and intraclass levels of divergence. These multiplicities allow conclusions on pathways of function for ADHs and suggest this activity to have two roles in addition to its function in metabolism, one of a basic defence nature, the other of regulatory value in higher eukaryotes. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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| 2. |
- Persson, Bengt, et al.
(author)
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Coenzyme-based functional assignments of short-chain dehydrogenases/reductases (SDRs)
- 2003
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In: Chemico-Biological Interactions. - 0009-2797 .- 1872-7786. ; 143-144, s. 271-278
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Conference paper (other academic/artistic)abstract
- Short-chain dehydrogenases/reductases (SDRs) are enzymes of great functional diversity. In spite of a residue identity of only 15-30%, the folds are conserved to a large extent, with specific sequence motifs detectable. We have developed an assignment scheme based on these motifs and detect five families. Only two of these were known before, called 'Classical' and 'Extended', but are now distinguished at a further level based on patterns of charged residues in the coenzyme-binding region, giving seven subfamilies of classical SDRs and three subfamilies of extended SDRs. Three further families are novel entities, denoted 'Intermediate', 'Divergent' and 'Complex', encompassing short-chain alcohol dehydrogenases, enoyl reductases and multifunctional enzymes, respectively. The assignment scheme was applied to the genomes of human, mouse, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae. In the animal genomes, genes corresponding to the extended SDRs amount to around one quarter or less of the total number of SDR genes, while in those of A. thaliana and S. cerevisiae, the extended members constitute about 40% of the SDR forms. The NAD(H)-dependent SDRs are about equally many as the NADP(H)-dependent ones in human, mouse and plant, while the proportions of NAD(H)-dependent enzymes are much lower in fruit fly, worm and yeast. We also find that NADP(H) is the preferred coenzyme among most classical SDRs, while NAD(H) is that preferred among most extended SDRs. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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| 27. |
- Bergander, Linda, et al.
(author)
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Metabolic fate of the Ah receptor ligand 6-formylindolo[3,2-b]carbazole
- 2004
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In: Chemico-Biological Interactions. - : Elsevier BV. - 0009-2797. ; 149:2-3, s. 151-164
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Journal article (peer-reviewed)abstract
- The physiological role of the aryl hydrocarbon receptor (AhR), a member of the basic helix-loop-helix PER-ARNT-SIM (PAS) transcription factor family is not known. We have suggested that the AhR is involved in light signaling through binding of photoproducts with high AhR affinity. This suggestion is based on (i) the high AhR affinity of the tryptophan photoproduct formylindolo[3,2-b]carbazole (FICZ), (ii) the induction of rapid and transient expression of AhR-regulated genes by FICZ and by extracts of UV-irradiated tryptophan as well as (iii) the fact that light induces the AhR-regulated cytochrome P450s CYP1A1, CYP1B1 and CYP2S1. The transient mRNA expression caused by light and tryptophan photoproducts suggests that the biotransformation enzymes induced by AhR activation take part in a metabolic degradation of the natural AhR ligand. This study aimed at identifying the involvement of phase I and phase II enzymes in the metabolic degradation of FICZ. A cytochrome P450-dependent metabolism of FICZ giving rise to preferentially mono- and di-hydroxylated derivatives has earlier been reported. In the present study, rat and human hepatic S9 mixes were employed together with specific enzyme inhibitors and cofactors. Compared to the Aroclor-induced rat liver S9, the non-induced rat liver S9 and the human liver S9 caused a more complex metabolite profile of FICZ. The CYP1A1 enzyme was confirmed to be the most important enzyme for the first step in the metabolism. CYP1A2 was found to have overlapping specificity with CYP1A1 being able to form the same major metabolites although with different kinetics. CYP1B1 turned out to be preferentially involved in the further metabolism of dihydroxylated metabolites. Microsomal epoxide hydrolase, and as yet not identified forms of sulphotransferases and glucuronosyltransferases were also found to take part in the metabolic degradation of FICZ. Thus, tryptophan photoproducts fit into a model in which the ligand-activated AhR signaling is autoregulated by the induced metabolic enzymes.
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| 30. |
- Dragani, B, et al.
(author)
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Role of conserved local motifs in folding and stability of hGSTP1-1
- 2001
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In: CHEMICO-BIOLOGICAL INTERACTIONS. - : ELSEVIER SCI IRELAND LTD. - 0009-2797. ; 133:1-3, s. 17-18
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Journal article (peer-reviewed)abstract
- We investigated, by site directed mutagenesis, the role played by a conserved N-capping box and hydrophobic staple motif in the folding and stability of human GSTPl-1. The corresponding mutants, I149A, S150A, D153A and Y154A, in which these motifs have be
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| 32. |
- Gardner, JL, et al.
(author)
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Characterization of a peptide antibody toward hGSTA4-4
- 2001
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In: CHEMICO-BIOLOGICAL INTERACTIONS. - : ELSEVIER SCI IRELAND LTD. - 0009-2797. ; 133:1-3, s. 63-67
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Journal article (peer-reviewed)abstract
- A polyclonal antibody was developed that can discriminate human alpha class glutathionetransferase 4-4 (hGSTA4-4). This was accomplished by first determining candidate peptide sequences of the hGSTA4 subunit, which exhibited low homology to other human GS
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- Jemth, P, et al.
(author)
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Ser11 plays several roles in the catalytic mechanism of rat glutathione transferase T2-2
- 2001
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In: CHEMICO-BIOLOGICAL INTERACTIONS. - : ELSEVIER SCI IRELAND LTD. - 0009-2797. ; 133:1-3, s. 178-181
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Journal article (peer-reviewed)abstract
- Ser11 in rat glutathione transferase T2-2 promotes several steps in the catalyzed reaction pathway of the enzyme. First, the residue lowers the pK(a) value of the enzyme-bound glutathione thiol by 2.2 pH units, from 7.9 to 5.7. Secondly, the presence of S
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- Nilsson, LO, et al.
(author)
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Structural basis for 4-hydroxyalkenal activity in human glutathione transferase A4-4
- 2001
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In: CHEMICO-BIOLOGICAL INTERACTIONS. - : ELSEVIER SCI IRELAND LTD. - 0009-2797. ; 133:1-3, s. 360-363
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Journal article (peer-reviewed)abstract
- The Alpha class glutathione transferase A4-4 (GST A4-4) detoxifies products of lipid peroxidation, e.g.4-hydroxynonenal, by a Michael-addition to glutathione. Another Alpha class enzyme, GST A1-1, is not as efficient although the structures of the enzymes
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