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1.
In this report we describe the main features of the initially determined alcohol dehydrogenase, that of horse liver, relate
this to the human enzyme structures and review recent structural studies on mutants and new complexes of the enzymes. We further
review the structure of a bacterial alcohol dehydrogenase to arrive at a coherent picture of medium-chain dehydrogenase/reductase
alcohol dehydrogenases in general. 相似文献
2.
B. Persson J. Hedlund H. Jörnvall 《Cellular and molecular life sciences : CMLS》2008,65(24):3879-3894
The MDR superfamily with ~350-residue subunits contains the classical liver alcohol dehydrogenase (ADH), quinone reductase,
leukotriene B4 dehydrogenase and many more forms. ADH is a dimeric zinc metalloprotein and occurs as five different classes
in humans, resulting from gene duplications during vertebrate evolution, the first one traced to ~500 MYA (million years ago)
from an ancestral formaldehyde dehydrogenase line. Like many duplications at that time, it correlates with enzymogenesis of
new activities, contributing to conditions for emergence of vertebrate land life from osseous fish. The speed of changes correlates
with function, as do differential evolutionary patterns in separate segments. Subsequent recognitions now define at least
40 human MDR members in the Uniprot database (corresponding to 25 genes when excluding close homologues), and in all species
at least 10888 entries. Overall, variability is large, but like for many dehydrogenases, subdivided into constant and variable
forms, corresponding to household and emerging enzyme activities, respectively. This review covers basic facts and describes
eight large MDR families and nine smaller families. Combined, they have specific substrates in metabolic pathways, some with
wide substrate specificity, and several with little known functions. 相似文献
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C. A. Staab M. Hellgren J.-O. Höög 《Cellular and molecular life sciences : CMLS》2008,65(24):3950-3960
Alcohol dehydrogenase 3 (ADH3) is highly conserved, ubiquitously expressed in mammals and involved in essential cellular pathways.
A large active site pocket entails special substrate specificities: shortchain alcohols are poor substrates, while medium-chain
alcohols and particularly the glutathione adducts S-hydroxymethylglutathione (HMGSH) and S-nitrosoglutathione (GSNO) are efficiently
converted under concomitant use of NAD+/NADH. By oxidation of HMGSH, the spontaneous glutathione adduct of formaldehyde, ADH3 is implicated in the detoxification
of formaldehyde. Through the GSNO reductase activity, ADH3 can affect the transnitrosation equilibrium between GSNO and S-nitrosated
proteins, arguing for an important role in NO homeostasis. Recent findings suggest that ADH3-mediated GSNO reduction and subsequent
product formation responds to redox states in terms of NADH availability and glutathione levels. Finally, a dual function
of ADH3 is discussed in view of its potential implications for asthma. 相似文献
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Zinc plays an important role in the structure and function of many enzymes, including alcohol dehydrogenases (ADHs) of the
MDR type (mediumchain dehydrogenases/reductases). Active site zinc participates in catalytic events, and structural site zinc
maintains structural stability. MDR-types of ADHs have both of these zinc sites but with some variation in ligands and spacing.
The catalytic zinc sites involve three residues with different spacings from two separate protein segments, while the structural
zinc sites involve four residues and cover a local segment of the protein chain (Cys97-Cys111 in horse liver class I ADH).
This review summarizes properties of both ADH zinc sites, and relates them to zinc sites of proteins in general. In addition,
it highlights a separate study of zinc binding peptide variants of the horse liver ADH structural zinc site. The results show
that zinc coordination of the free peptide differs markedly from that of the enzyme (one His / three Cys versus four Cys),
suggesting that the protein zinc site is in an energetically strained conformation relative to that of the peptide. This finding
is a characteristic of an entatic state, implying a functional nature for this zinc site. 相似文献
8.
Shafqat N Shafqat J Eissner G Marschall HU Tryggvason K Eriksson U Gabrielli F Lardy H Jörnvall H Oppermann U 《Cellular and molecular life sciences : CMLS》2006,63(10):1205-1213
Human Hep27 was originally isolated from growth-arrested HepG2 cells and identified as a member of the superfamily of short-chain
dehydrogenases/reductases (SDR). Its substrate specificity has not been determined, but a cross-species comparison suggests
that it occurs in widely divergent species, such as human, Cenorhabditis elegans, Drosophila and Arabidopsis thaliana. In this study, Hep27 was expressed as a His6 fusion protein, and subjected to a substrate screen, using a compound library of SDR substrates, comprising steroids, retinoids,
sugars and carbonyl compounds. Whereas no steroid dehydrogenase or retinoid activity was detected, it was found that Hep27
catalyzed the NADPH-dependent reduction of dicarbonyl compounds, like 3,4-hexanedione and 1-phenyl-1,2-propanedione with similar
turnover numbers as DCXR (a mitochondrial dicarbonyl reductase/xylulose reductase). In contrast, Hep27 does not convert sugar
substrates like xylulose or threose. Based on its substrate specificity and expression in endothelial tissues, it is suggested
that Hep27 functions as a dicarbonyl reductase in enzymatic inactivation of reactive carbonyls, involved in covalent modification
of cellular components.
Received 16 January 2006; received after revision 28 February 2006; accepted 31 March 2006 相似文献
9.
Hirschberg D Cederlund E Crosas B Jonsson A Tryggvason S Farrés J Parés X Bergman T Jörnvall H 《Cellular and molecular life sciences : CMLS》2001,58(9):1323-1326
A recent finding of a novel class of retinol-active alcohol dehydrogenase (ADH) in frog prompted analysis of this activity in other vertebrate forms. Surprisingly, yet another and still more unrelated ADH was identified in chicken tissues. It was found to be a member of the aldo-keto reductase (AKR) enzyme family, not previously known as an ADH in vertebrates. Its terminal blocking group and the N-terminal segment, not assigned by protein and cDNA structure analysis, were determined by electrospray tandem mass spectrometry after protein isolation by two-dimensional gel electrophoresis. The N terminus is Acetyl-Ala- and the N-terminal segment contains two consecutive Asn residues. The results establish the new ADH enzyme of the AKR family and show the usefulness of combined gel separation and mass spectrometry in enzyme-characterization. 相似文献
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S-nitrosoglutathione (GSNO) formation represents a mechanism for storage and transport of nitric oxide. Analysis of human liver and Saccharomyces cerevisiae extracts has revealed the presence of only one enzyme able to significantly reduce GSNO, identified as glutathione-dependent formaldehyde dehydrogenase (FALDH). GSNO is the best substrate known for the human and yeast enzymes (kcat/Km = 444,400 and 350,000 mM(-1) min(-1), respectively). Although NADH is the preferred cofactor, some activity with NADPH (Km = 460 microM) can be predicted in vivo. The subcellular localization demonstrates a cytosolic and nuclear distribution of FALDH in living yeast cells. This agrees with previous results in rat, and suggests a role in the regulation of GSNO levels in the cytoplasmic and nuclear compartments of the eukaryotic cell. 相似文献
12.
Mammalian heat shock protein families. Expression and functions. 总被引:2,自引:0,他引:2
13.
H. S. Yong K. L. Chan C. Mak S. S. Dhaliwal 《Cellular and molecular life sciences : CMLS》1981,37(2):130-131
Summary Isocitrate dehydrogenase (E.C. 1.1.1.42) gene duplication was demonstrated in the self-pollinated soybean (Glycine max) by means of starch-gel electrophoresis. This finding explains the heterogeneity and/or fixed heterophenotype observed in some soybean cultivars. 相似文献
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Anna Maria Frassanito Laura Barsanti Vincenzo Passarelli Valtere Evangelista Paolo Gualtieri 《Cellular and molecular life sciences : CMLS》2010,67(6):965-971
Here, we report the DNA sequence of the rhodopsin gene in the alga Cyanophora paradoxa (Glaucophyta). The primers were designed according to the conserved regions of prokaryotic and eukaryotic rhodopsin-like
proteins deposited in the GenBank. The sequence consists of 1,272 bp comprised of 5 introns. The correspondent protein, named
Cyanophopsin, showed high identity to rhodopsin-like proteins of Archea, Bacteria, Fungi, and Algae. At the N-terminal, the
protein is characterized by a region with no transmembrane α-helices (80 aa), followed by a region with 7α-helices (219 aa)
and a shorter 35-aa C-terminal region. The DNA sequence of the N-terminal region was expressed in E. coli and the recombinant purified peptide was used as antigen in hens to obtain polyclonal antibodies. Indirect immunofluorescence
in C. paradoxa cells showed a marked labeling of the muroplast (aka cyanelle) membrane. 相似文献
16.
Karen Bush Joan S. Freudenberger Dorothy S. Slusarchyk R. B. Sykes E. Meyers 《Cellular and molecular life sciences : CMLS》1982,38(4):436-437
Summary Growth ofCandida albicans can be inhibited by sulfa drugs which prevent biosynthesis of folic acid. The dihydrofolate reductase (E.C. 1.5.1.3) inhibitors aminopterin and methotrexate also exhibit anticandidal activity, but trimethoprim does not. Kinetic evaluations withC. albicans dihydrofolate reductase indicate that methotrexate and aminopterin are tight-binding inhibitors whereas trimethoprim binds poorly. 相似文献
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S. M. Houten M. Chegary H. te Brinke W. J. Wijnen J. F. C. Glatz J. J. F. P. Luiken F. A. Wijburg R. J. A. Wanders 《Cellular and molecular life sciences : CMLS》2009,66(7):1283-1294
Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose
is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose
oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate
dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We
show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration
synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of
peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose
oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status
in order to spare glucose.
S. M. Houten, M. Chegary: These two authors contributed equally to this work.
Received 11 July 2008; received after revision 26 January 2009; accepted 02 February 2009 相似文献
19.
Heat shock protein gene expression during Xenopus development 总被引:2,自引:0,他引:2
J. J. Heikkila N. Ohan Y. Tam A. Ali 《Cellular and molecular life sciences : CMLS》1997,53(1):114-121
Stress-induced heat shock protein gene expression is developmentally regulated during early embryogen esis of the frog, Xenopus laevis. For example, a number of heat shock protein genes, such as hsp70,
hsp90, and ubiquitin are not heat-inducible until after the midblastula stage of embryogenesis. Furthermore, the family of small heat shock protein
genes, hsp30, are differentially expressed after the midblastula stage as well as being regulated at the level of mRNA stability. Many
of these stress proteins are also synthesized constitutively during oogenesis and embryogenesis during which they may act
as molecular chaperones as well as being involved in sequestering proteins in an inactive state until required by the developing
embryo. Furthermore the induction of these stress protein genes has been correlated with enhanced thermoresistance. During
stressful conditions heat shock proteins probably prevent aggregation or misfolding of damaged protei
ns within the embryo. 相似文献