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1.
Abstract: A series of l-phenyl-1 H -3-benzazepine analogues were assessed for enantiomeric and structure-affinity relationships at human putamen D-1 dopamine receptors labelled with [3 H]SCH 23390. Substitution at the 7-position of both 3-H and 3-methyl benzazepine molecules critically affected affinity for these receptors over a 500-fold range. The general rank order of potency of 7-substituents was Cl = Br ≫ CH3 > OH ≥ H. 3-Methyl substituents increased the affinity of 7-H and 7-OH compounds two- to fivefold compared to desmethyl counterparts. The displacement of [3 H]SCH 23390 binding showed substantial enantioselec-tivity; the R-enantiomer of SKF 83566 was 500-fold more potent that its S-antipode. However, the displacement of [3 H]spiperone binding from D-2 sites in the same tissue showed negligible enantioselectivity. Through such structure-affinity relationships, these studies may help to define the topography of the human brain D-1 dopamine receptor and guide the design of more selecive agents for functional studies. 相似文献
2.
Youngdo Won Richard A. Friesner Martin R. Johnson Jonathan L. Sessler 《Photosynthesis research》1989,22(3):201-210
The Soret absorption spectra of six synthetic rigid porphyrin dimers whose crystal structures have been determined are simulated using simple exciton theory. The objective is to test the validity of the point dipole and associated approximations; the electronic interaction parameters are thus calculated using data obtained from the monomer spectra, with no adjustable parameters. Satisfactory agreement between theory and experiment is obtained for one class of dimers but not for a second. This poses a challenge for semiempirical electronic structure methods as to whether improvements over the point dipole calculations can be obtained. 相似文献
3.
Kunio Yonemasu Takako Sasaki Yoshiko Dohi Charles M. Lapière Betty Nusgens 《生物化学与生物物理学报:疾病的分子基础》1990,1096(1):47-51
C1q, a collagen-like complement protein, was purified from the serum of a ddermatosparactic calf which lacks procollagen N-terminal proteinase (pN-proteinase). The specific hemolytic activity of the serum Clq from the dermatosparactic animal was identical to that of C1q from a normal calf. Gel-filtration of serum from dermatosparactic calf, on Sepharose 6B, showed the presence of C1q-antigenic material at only one position which was identical to the elution position of normal bovine C1q. No differdence, under dissociating conditions, could be seen in the size of the chains of C1q in specific immunoprecipitates isolated from the sera of dermatosparactic and normal animals, as judged by polyacrylamidegel electrophoresis (PAGE) in the presence of sodium dodecyl sulfate (SDS). The C1q from the dermatosparactic animal showed the same N-terminal amino acid and typtic-digest peptide pattern on HPLC as C1q from the normal calf. These results strongly suggest that pN-proteinase is not involved in the extracellular processing of C1q. 相似文献
4.
Urs Kägi James G. Chafouleas Anthony W. Norman Dr. Claus W. Heizmann 《Cell and tissue research》1988,252(2):359-365
Summary Calcium and intracellular Ca2+-binding proteins are possibly involved in hormone production and spermatogenesis in rat testis. Parvalbumin, calbindin D-28K, S-100 proteins and calmodulin were localized in the Leydig cells, which are sites of testosterone synthesis. Only the appearance of parvalbumin-immunoreactivity is closely correlated to testosterone production during development of the testes. Calbindin D-28K-immunoreactivity persisted in foetal-type Leydig cells and in adult-type Leydig cells at all stages of development. S-100-immunoreactivity was low during all foetal stages, absent between birth and puberty, and increased thereafter. Calmodulin staining is most prominent in the cytoplasm of developing spermatocytes and of maturing spermatids. All four proteins co-exist in the seminiferous tubules. The distinct localization and developmental appearance of these proteins suggests different regulatory roles in Leydig cell function and spermatogenesis. 相似文献
5.
A. M. N. Sultan 《Molecular and cellular biochemistry》1992,113(1):17-23
This work investigates the effect of alloxan-induced short-term diabetes (24 h) on D-3-hydroxybutyrate metabolism at physiological
and non-physiological concentrations of the ketone body in the isolated non-working perfused rat heart. Also the effect of
insulin (2 mU.ml−1) on D-3-hydroxybutyrate metabolism was investigated in hearts from normal and diabetic rats. The rates of D-3-hydroxybutyrate
utilization and oxidation and of acetoacetate production were proportional to D-3-hydroxybutyrate concentration. The utilization
of D-3-hydroxybutyrate showed saturation kinetics in hearts from normal and diabetic rats, in the presence and absence of
insulin. Acute short-term diabetes augmented D-3-hydroxybutyrate utilization and oxidation at 1.25 and 2.5 mM DL-3-HB, with
no significant effect at higher concentrations, but increased acetoacetate production at all investigated concentrations.
In hearts from normal rats, insulin enhanced D-3-hydroxybutyrate utilization and oxidation at 2.5, 5, and 10 mM DL-3-HB, but
no effect was observed at the lowest (1.25 mM) and highest (16 mM) DL-3-HB concentrations. Insulin had no effect on D-3-hydroxybutyrate
metabolism in hearts from diabetic rats. No significant effect of insulin on the rate of acetoacetate production in normal
and diabetic states was observed. 相似文献
6.
[3H]Piflutixol binding to rat striatal membrane preparations identifies both D-1 and D-2 sites. We used [3H]piflutixol to characterise those binding sites present in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)-solubilised rat striatal preparations. The specific binding of [3H]piflutixol, as defined using cis-flupenthixol, to CHAPS-solubilised rat striatal tissue was saturable and of high affinity. Specific [3H]piflutixol binding to the solubilised preparations was displaced stereoselectively by the isomers of butaclamol and to an equal extent by both cis-flupenthixol and (+/-)-sulpiride. A positive correlation was found between the capacity of a range of drugs to displace [3H]piflutixol binding and the displacement of [3H]spiperone to the same preparations. The Bmax of [3H]piflutixol binding was not different from that of [3H]spiperone binding to the same preparation. These studies suggest that, in contrast to specific binding of membrane preparations, the specific binding of [3H]piflutixol to CHAPS-solubilised preparations involves mainly D-2 sites. Specific [3H]piflutixol binding, in contrast to [3H]spiperone binding, showed only slow dissociation from soluble preparations. The binding of [3H]piflutixol to CHAPS-solubilised preparations was retained during passage through a gel filtration column. This prelabelling of solubilised striatal preparations using [3H]piflutixol may aid in the purification of CHAPS-solubilised rat striatal D-2 sites. 相似文献
7.
M. Rosa Pinol Urs Kägi Claus W. Heizmann Brigitte Vogel Jean-Marc Séquier Werner Haas Willi Hunziker 《Journal of neurochemistry》1990,54(6):1827-1833
Many processes in the CNS depend on calcium. The calcium signal is transduced into an intracellular response via Ca2(+)-binding proteins, including calbindin D-28K. In many laboratories, polyclonal antibodies against chicken intestinal calbindin D-28K have been used to study its localization in the brain (normal and degenerated) of various species, including humans, but some of these antisera cross-reacted with other proteins, including calretinin. We purified recombinant rat brain calbindin D-28K to raise antisera in rabbits and purified a recombinant rat-chicken calbindin D-28K hybrid protein to immunize mice for the generation of monoclonal antibodies. These antisera were highly specific for calbindin D-28K, as demonstrated by two-dimensional Western blotting analysis. Immunohistochemical analyses combined with in situ hybridization studies demonstrated that calbindin D-28K in the Purkinje cells of the cerebellum is independent of vitamin D. The antibodies described here will be important tools for studying the regulation of expression of calbindin D-28K and its biological function in the brain and in the PNS. 相似文献
8.
Summary We first present two simple dimeric models of cotransport that may account for all of the kinetics of Na++-d-glucose cotransport published so far in the small intestine. Both the sigmoidicity in the Na++ activation of transport (positive cooperativity) and the upward deviations from linearity in the Eadie-Hofstee plots relative to glucose concentrations (negative cooperativity) can be rationalized within the concept of allosteric kinetic mechanisms corresponding to either of two models involving sequential or mixed concerted and sequential conformational changes. Such models also allow for 2 Na++ 1 S and 1 Na++ 1 S stoichiometries of cotransport at low and high substrate concentrations, respectively, and for partial inhibition by inhibitors or substrate analogues. Moreover, it is shown that the dimeric models may present physiological advantages over the seemingly admitted hypothesis of two different cotransporters in that tissue. We next address the reevaluation of Na++-d-glucose cotransport kinetics in rabbit intestinal brush border membrane vesicles using stable membrane preparations, a dynamic approach with the Fast Sampling Rapid Filtration Apparatus (FSRFA), and both nonlinear regression and statistical analyses. Under different conditions of temperatures, Na++ concentrations, and membrane potentials clamped using two different techniques, we demonstrate that our data can be fully accounted for by the presence of only one carrier in rabbit jejunal brush border membranes since transport kinetics relative to glucose concentrations satisfy simple Michaelis-Menten kinetics. Although supporting a monomeric structure of the cotransporter, such a conclusion would conflict with previous kinetic data and more recent studies implying a polymeric structure of the carrier protein. We thus consider a number of alternatives trying to reconcile the observation of Michaelis-Menten kinetics with allosteric mechanisms of cotransport associated with both positive and negative cooperativities for Na++ and glucose binding, respectively. Such models, implying energy storage and release steps through conformational changes associated with ligand binding to an allosteric protein, provide a rational hypothesis to understand the long-time debated question of energy transduction from the Na++ electrochemical gradient to the transporter.This research was supported by grant MT-7607 from the Medical Research Council of Canada. One of the authors (A.B.) was supported by a scholarship from the Fonds de la Recherche en Santé du Québec and C. C. was supported by a fellowship from the GRTM. The technical assistance of Mrs. C. Leroy has been greatly appreciated. The authors also thank D.D. Maenz and C. Malo for insightful discussions and C. Gauthier for the art work. 相似文献
9.
S. Cusack 《Biochimie》1993,75(12)
The seven class 2 aminoacyl-tRNA synthetases that are α2 dimers have previously been divided by sequence homology into class 2a (seryl-, threonyl-, prolyl- and histidyl-) and class 2b (aspartyl-, asparaginyl- and lysyl-). It has been more difficult to classify the glycyl-, phenylalanyl- and alanyl-tRNA synthetases which have different subunit stoichiometries and which did not apparently contain all three canonical class 2 motifs. New sequence and structural information relating to the three problematic synthetases will be discussed permitting a step forward to be taken in the understanding of the evolutionary relationships between the class 2 synthetases. 相似文献
10.
Comparison of the crystal structures of genetically engineered human manganese superoxide dismutase and manganese superoxide dismutase from Thermus thermophilus: differences in dimer-dimer interaction. 下载免费PDF全文
U. G. Wagner K. A. Pattridge M. L. Ludwig W. C. Stallings M. M. Werber C. Oefner F. Frolow J. L. Sussman 《Protein science : a publication of the Protein Society》1993,2(5):814-825
The three-dimensional X-ray structure of a recombinant human mitochondrial manganese superoxide dismutase (MnSOD) (chain length 198 residues) was determined by the method of molecular replacement using the related structure of MnSOD from Thermus thermophilus as a search model. This tetrameric human MnSOD crystallizes in space group P2(1)2(1)2 with a dimer in the asymmetric unit (Wagner, U.G., Werber, M.M., Beck, Y., Hartman, J.R., Frolow, F., & Sussman, J.L., 1989, J. Mol. Biol. 206, 787-788). Refinement of the protein structure (3,148 atoms with Mn and no solvents), with restraints maintaining noncrystallographic symmetry, converged at an R-factor of 0.207 using all data from 8.0 to 3.2 A resolution and group thermal parameters. The monomer-monomer interactions typical of bacterial Fe- and Mn-containing SODs are retained in the human enzyme, but the dimer-dimer interactions that form the tetramer are very different from those found in the structure of MnSOD from T. thermophilus. In human MnSOD one of the dimers is rotated by 84 degrees relative to its equivalent in the thermophile enzyme. As a result the monomers are arranged in an approximately tetrahedral array, the dimer-dimer packing is more intimate than observed in the bacterial MnSOD from T. thermophilus, and the dimers interdigitate. The metal-ligand interactions, determined by refinement and verified by computation of omit maps, are identical to those observed in T. thermophilus MnSOD. 相似文献