共查询到20条相似文献,搜索用时 15 毫秒
1.
Mikko Hellgren Jonas Carlsson Linus J. Östberg Claudia A. Staab Bengt Persson Jan-Olov Höög 《Cellular and molecular life sciences : CMLS》2010,67(17):3005-3015
Alcohol dehydrogenase 3 (ADH3) has been assigned a role in nitric oxide homeostasis due to its function as an S-nitrosoglutathione reductase. As altered S-nitrosoglutathione levels are often associated with disease, compounds that modulate ADH3 activity might be of therapeutic
interest. We performed a virtual screening with molecular dockings of more than 40,000 compounds into the active site of human
ADH3. A novel knowledge-based scoring method was used to rank compounds, and several compounds that were not known to interact
with ADH3 were tested in vitro. Two of these showed substrate activity (9-decen-1-ol and dodecyltetraglycol), where calculated
binding scoring energies correlated well with the logarithm of the k
cat/K
m values for the substrates. Two compounds showed inhibition capacity (deoxycholic acid and doxorubicin), and with these data
three different lines for specific inhibitors for ADH3 are suggested: fatty acids, glutathione analogs, and cholic acids. 相似文献
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Zusammenfassung Neben zwei elektrophoretisch verschiedenen Varianten derDrosophila-Alkoholdehydrogenase kommen innerhalb dieser Varianten weitere Variationen vor, die sich in ihrer spezifischen Aktivität und Temperaturempfindlichkeit unterscheiden. Es wird daraus geschlossen, dass der Grad des Polymorphismus von Populationen grösser sei, als aufgrund elektrophoretischer Untersuchungen geschätzt wird. 相似文献
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R. B. Imberski W. H. Sofer H. Ursprung 《Cellular and molecular life sciences : CMLS》1968,24(5):504-505
Zusammenfassung
Drosophila besitzt Alkoholdehydrogenase in mehreren elektrophoretisch trennbaren molekularen Formen. Durch Anwendung von Acrylamid-Elektrophorese bei 2 verschiedenen Gel-Konzentrationen haben wir nachgewiesen, dass diese verschiedenen Isozyme sich nicht in ihrer Molekulargrösse unterscheiden und deshalb nicht Aggregate darstellen.
Work supported by NIH Training Grant No. HD 139-01 and NSF Grant No. GB-4451. 相似文献
Work supported by NIH Training Grant No. HD 139-01 and NSF Grant No. GB-4451. 相似文献
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Hjelmqvist L Norin A El-Ahmad M Griffiths W Jörnvall H 《Cellular and molecular life sciences : CMLS》2003,60(9):2009-2016
Alcohol dehydrogenases (ADHs) of the MDR type (medium-chain dehydrogenases/reductases) have diverged into two evolutionary groups in eukaryotes: a set of 'constant' enzymes (class III) typical of basal enzymes, and a set of 'variable' enzymes (remaining classes) suggesting 'evolving' forms. The variable set has larger overall variability, different segment variability, and variability also in functional segments. Using a major aldehyde dehydrogenase (ALDH) from cod liver and fish ALDHs deduced from the draft genome sequence of Fugu rubripes (Japanese puffer fish), we found that ALDHs form more complex patterns than the ADHs. Nevertheless, ALDHs also group into 'constant' and 'variable' sets, have separate segment variabilities, and distinct functions. Betaine ALDH (class 9 ALDH) is 'constant,' has three segments of variability, all non-functional, and a limited fish/human divergence, reminiscent of the ADH class III pattern. Enzymatic properties of fish betaine ALDH were also determined. Although all ALDH patterns are still not known, overall patterns are related to those of ADH, and group separations may be distinguished. The results can be interpreted functionally, support ALDH isozyme distinctions, and assign properties to the multiplicities of the ADH and ALDH enzymes. 相似文献
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Summary 4 forms of mutarotase from human kidney were demonstrated by DEAE-cellulose column chromatography. A major form of them was purified to homogeneity. 相似文献
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Hellgren M Strömberg P Gallego O Martras S Farrés J Persson B Parés X Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(4):498-505
The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2
(ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with
an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities
were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup.
This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic
retinol oxidation at physiological concentrations.
Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007 相似文献
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U. C. Dubach 《Cellular and molecular life sciences : CMLS》1965,21(5):263-263
Zusammenfassung In den einzelnen Abschnitten des menschlichen Nephrons und in Nierenhomogenaten wurden quantitativ die Glucose-6-phosphat-dehydrogenase-und
die Isozitronens?uredehydrogenase-Aktivit?t gemessen.
This investigation was made possible by a grant from the Swiss National Foundation for the Development of Scientific Research. The technical assistance of MissD. Keller is gratefully acknowledged. 相似文献
This investigation was made possible by a grant from the Swiss National Foundation for the Development of Scientific Research. The technical assistance of MissD. Keller is gratefully acknowledged. 相似文献
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Jessica Rodgers Stuart N. Peirson Steven Hughes Mark W. Hankins 《Cellular and molecular life sciences : CMLS》2018,75(19):3609-3624
Melanopsin is a blue light-sensitive opsin photopigment involved in a range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within the human melanopsin gene (OPN4), yet it remains unclear how these variants affect melanopsin protein function and downstream physiological responses to light. Here, we have used bioinformatic analysis and in vitro expression systems to determine the functional phenotypes of missense human OPN4 variants. From 1242 human OPN4 variants collated in the NCBI Short Genetic Variation database (dbSNP), we identified 96 that lead to non-synonymous amino acid substitutions. These 96 missense mutations were screened using sequence alignment and comparative approaches to select 16 potentially deleterious variants for functional characterisation using calcium imaging of melanopsin-driven light responses in HEK293T cells. We identify several previously uncharacterised OPN4 mutations with altered functional properties, including attenuated or abolished light responses, as well as variants demonstrating abnormal response kinetics. These data provide valuable insight into the structure–function relationships of human melanopsin, including several key functional residues of the melanopsin protein. The identification of melanopsin variants with significantly altered function may serve to detect individuals with disrupted melanopsin-based light perception, and potentially highlight those at increased risk of sleep disturbance, circadian dysfunction, and visual abnormalities. 相似文献
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Yang SJ Huh JW Lee JE Choi SY Kim TU Cho SW 《Cellular and molecular life sciences : CMLS》2003,60(11):2538-2546
Aluminum inactivated glutamate dehydrogenase (GDH) by a pseudo-first-order reaction at micromolar concentrations. A double-reciprocal plot gave a straight line with a kinact of 2.7 min-1 and indicated the presence of a binding step prior to inactivation. The inactivation was strictly pH dependent and a marked increase in sensitivity to aluminum was observed as the pH decreased. At a pH higher than 8.5, no inactivation was observed. The completely inactivated GDH contained 2 mol of aluminum per mole of enzyme subunit monomer. When preincubated with enzyme, several chelators such as citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or ethylenediaminetriacetic acid efficiently protected the enzyme against the aluminum inactivation. In a related experiment, only citrate and NaF released the aluminum from the completely inactivated aluminum-enzyme complex and fully recovered the enzyme activity. Ferritin, NADP+, or nerve growth factor did not show any effects on the recovery of the aluminum-inactivated GDH activity. The dissociation constant for the aluminum-enzyme complex was calculated to be 5.3 M. Although aluminum has been known to form a complex with nucleotides, no such effects were observed in the inactivation of GDH by aluminum as determined using GDHs mutated at the ADP-binding site, NAD+-binding site or GTP-binding site. Circular dichroism studies showed that the binding of aluminum to the enzyme induced a decrease in helices and sheets and an increase in random coil. Therefore, inactivation of GDH by aluminum is suggested to be due to the conformational change induced by aluminum binding. These results suggest a possibility that aluminum-induced alterations in enzymes of the glutamate system may be one of the causes of aluminum-induced neurotoxicity.Received 25 July 2003; received after revision 27 August 2003; accepted 15 September 2003 相似文献
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R Salvayre A Maret A Nègre L Douste-Blazy 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1979,288(12):995-998
1. Normal human leukocytes present three molecular forms of alpha-galactosidase (EC 3.2.1.22) separated using electrofocusing: a new major form IV (pI 4.0) characteristic of leukocytes and two forms that exist in other tissues, form I (pI 4.5) and form II (pI 4.0). 2. Normal human leukocytes present only one molecular form (pI 4.5) of N-acetyl-alpha-galactosaminidase (EC 3.2.1.49) corresponding to alpha-galactosidase form II. 3. In leukocytes from patients with Fabry disease, the electrofocusing shows that the alpha-galactosidase lacking corresponds to forms I and IV, while the residual activity corresponds to form II (or N-acetyl-alpha-galactosaminidase). 相似文献
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Chromatography on phosphocellulose revealed the existence of two well-separable forms of skeletal muscle AMP-deaminase in the tissue extracts of 11- and 16-week-old human fetuses. One of these forms elutes from the column at the same salt concentration as the muscle isozyme found in the skeletal muscle extract from adult man, and seems to have similar kinetic properties. The second form, which was found only in vestigial amounts in adult human tissue extract, represents different kinetic properties and seems to be a form characteristic for the fetal period of ontogenesis. 相似文献
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Summary Female choice mating experiments showed virgin femaleD. melanogaster of the 3Adh genotypes chose heterozygous (Adh
F
/Adh
S
) males most commonly. Inseminated females chose mates randomly, but the likelihood of a female remating was genotypically dependent.Acknowledgment. Financial support was provided by the Australian Research Grants Commitee. 相似文献