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101.
The polypeptides integrating amaranth globulin-p and 11S-globulin were characterized by two-dimensional electrophoresis, ion-exchange
chromatography and RP-HPLC. All polypeptides exhibited charge and hydrophobic heterogeneity. Almost all acid (A, pI 5–7) and
basic (B, pI 9–10) polypeptides were present in both globulins, and the same happened with the unprocessed M polypeptides
with pI in the range of 7–7.5 which fits well with a sequence containing both the A and B polypeptides. There were other polypeptides
only present in 11S-globulin, like some of 41 and 16 kDa, which might come from another precursor or be the products of a
different processing of the propolypeptide. These results suggested that, although amaranth subunits from different subfamilies
are interchangeable in different oligomers, some structural differences between them might affect the assembly of globulin
molecules. Structural differences arising from this behavior could account for the different physicochemical properties of
globulin molecules. 相似文献
102.
Hoppen J Dietz M Warsow G Rohde R Schüller HJ 《Molecular genetics and genomics : MGG》2007,278(3):317-330
103.
The high incidence of thrombembolic diseases justifies the development of new antithrombotics. The search for a direct inhibitor has resulted in the synthesis of a considerable number of low molecular weight molecules that inhibit human α-thrombin potently. However, efforts to develop an orally active drug remain in progress as the most active inhibitors with a highly basic P1 moiety exhibit an unsatisfactory bioavailability profile. In our previous work we solved several X-ray structures of human α-thrombin in complexes with (1) novel bicyclic arginine mimetics attached to the glycylproline amide and pyridinone acetamide scaffold and (2) inhibitors with a novel aza scaffold and with charged or neutral P1 moieties. In the present contribution, we correlate the structures of the complex between these inhibitors and the protein with the calculated free energy of binding. The energy of solvation was calculated using the Poisson–Boltzmann approach. In particular, the requirements for successful recognition of an inhibitor at the protein’s active site pocket S1 are discussed.
Figure We report here on free energy of binding analysis of thrombin inhibitors with novel aza scaffold and novel bicyclic arginine mimetics in S1 pocket of thrombin 相似文献
104.
Herrera-Camacho I Rosas-Murrieta NH Rojo-Domínguez A Millán L Reyes-Leyva J Santos-López G Suárez-Rendueles P 《The FEBS journal》2007,274(23):6228-6240
A new leucyl aminopeptidase activity has been identified in the fission yeast Schizosaccharomyces pombe. The enzyme, which has been purified and named leucyl aminopeptidase yspII (LAP yspII), had a molecular mass of 320 and 54 kDa by gel filtration and SDS/PAGE, respectively, suggesting a homohexameric structure. The enzyme cleaved synthetic aminoacyl-4-nitroanilides at an optimum of pH 8.5, and preferred leucine and methionine as N-terminal amino acids. A clear dependence on Mn2+ concentration for activity was found, and an apparent association constant of 0.33 mM was calculated for the metal ion. Bestatin behaved as a competitive inhibitor of LAP yspII (K(i) = 0.14 microM), while chelating agents such as chloroquine, EDTA and 1,10-phenanthroline also reduced enzyme activity. A MALDI-MS analysis, followed by sequencing of two of the resulting peptides, showed that LAP yspII undoubtedly corresponds to the putative aminopeptidase C13A11.05 identified in the S. pombe genome project. The protein exhibited nearly 40% sequence identity to fungal and mammalian aminopeptidases belonging to the M17 family of metallopeptidases. Catalytic residues (Lys292 and Arg366), as well as those involved in coordination with the cocatalytic metal ions (Lys280, Asp285, Asp303, Asp362 and Glu364) and those forming the hydrophobic pocket for substrate binding (Met300, Asn360, Ala363, Thr390, Leu391, Ala483 and Met486), were perfectly conserved among all known aminopeptidases. The S. pombe enzyme is predicted to be formed two clearly distinguished domains with a well conserved C-terminal catalytic domain showing a characteristic topology of eight beta-sheets surrounded by alpha-helical segments in the form of a saddle. 相似文献
105.
Nora N. Hanson Gordon W. Smith Stuart J. Middlemas Christopher D. Todd 《Journal of fish biology》2019,94(1):183-186
Using tagged and recaptured Atlantic salmon Salmo salar (n = 106) the present analysis shows that the most commonly applied linear back-calculation method for estimating past length, the Dahl-Lea method, resulted in overestimation of the length of large smolts and underestimation of small smolts. A correction equation (y = 0.53x + 6.23) for estimating true smolt length (y) from lengths back-calculated from adult scale measures (x) to account for these systematic discrepancies is proposed. 相似文献
106.
Hans-Joachim Gregor 《Feddes Repertorium》1982,93(5):351-362
In contrast to the opinion of Miki (1952 b, p. 349) the genus Hemitrapa Miki (Trapellaceae) is not only found in Asia and America but also in Europe. Wrongly determined fossils of the type „Trapa silesiaca Goeppert”︁ (the original species from Schoßnitz in Poland is under research by M. Lancucka-Srodoniowa, Krakow) belong to the genus Hemitrapa Miki. Some other Bavarian fossils are newly decribed here as Hemitrapa heissigii sp. nov. Hemitrapa fossils grew not only in the Senftenberg area (Menzel 1906), in Silesia (Kräusel 1920) or the Niederlausitz area (Menzel in Gothan & Sapper 1933), at Konin (Raniecka-Bobrowska 1954), but possibly also near Cologne (Kilpper 1969 and Kramer 1974) and at Ponholz (Gregor 1980). Especially in the Middle Miocene Upper Freshwater Molasse of Bavaria the fossil species Hemitrapa heissigii is found in numerous specimens near Eberstetten, Haag a. d. Amper and Rauscheröd (all in southern Bavaria). Hemitrapa heissigii can be used as an index-fossil and signs Uppermost Miocene sediments (Badenian, Samartian). The occurence in Pliocene localities is to be prooved. The whole group around Hemitrapa is considered to be a “late element” (Upper Miocene) in Europe. 相似文献
107.
Yurong Cheng Yong Li Nora Scherer Franziska Grundner-Culemann Terho Lehtimki Binisha H. Mishra Olli T. Raitakari Matthias Nauck Kai-Uwe Eckardt Peggy Sekula Ulla T. Schultheiss 《PLoS genetics》2022,18(4)
Osteopontin (OPN), encoded by SPP1, is a phosphorylated glycoprotein predominantly synthesized in kidney tissue. Increased OPN mRNA and protein expression correlates with proteinuria, reduced creatinine clearance, and kidney fibrosis in animal models of kidney disease. But its genetic underpinnings are incompletely understood. We therefore conducted a genome-wide association study (GWAS) of OPN in a European chronic kidney disease (CKD) population. Using data from participants of the German Chronic Kidney Disease (GCKD) study (N = 4,897), a GWAS (minor allele frequency [MAF]≥1%) and aggregated variant testing (AVT, MAF<1%) of ELISA-quantified serum OPN, adjusted for age, sex, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) was conducted. In the project, GCKD participants had a mean age of 60 years (SD 12), median eGFR of 46 mL/min/1.73m2 (p25: 37, p75: 57) and median UACR of 50 mg/g (p25: 9, p75: 383). GWAS revealed 3 loci (p<5.0E-08), two of which replicated in the population-based Young Finns Study (YFS) cohort (p<1.67E-03): rs10011284, upstream of SPP1 encoding the OPN protein and related to OPN production, and rs4253311, mapping into KLKB1 encoding prekallikrein (PK), which is processed to kallikrein (KAL) implicated through the kinin-kallikrein system (KKS) in blood pressure control, inflammation, blood coagulation, cancer, and cardiovascular disease. The SPP1 gene was also identified by AVT (p = 2.5E-8), comprising 7 splice-site and missense variants. Among others, downstream analyses revealed colocalization of the OPN association signal at SPP1 with expression in pancreas tissue, and at KLKB1 with various plasma proteins in trans, and with phenotypes (bone disorder, deep venous thrombosis) in human tissue. In summary, this GWAS of OPN levels revealed two replicated associations. The KLKB1 locus connects the function of OPN with PK, suggestive of possible further post-translation processing of OPN. Further studies are needed to elucidate the complex role of OPN within human (patho)physiology. 相似文献
108.
Andre Bazzone Laura Tesmer Derya Kurt H. Ronald Kaback Klaus Fendler M. Gregor Madej 《The Journal of biological chemistry》2022,298(2)
Bacterial transporters are difficult to study using conventional electrophysiology because of their low transport rates and the small size of bacterial cells. Here, we applied solid-supported membrane–based electrophysiology to derive kinetic parameters of sugar translocation by the Escherichia coli xylose permease (XylE), including functionally relevant mutants. Many aspects of the fucose permease (FucP) and lactose permease (LacY) have also been investigated, which allow for more comprehensive conclusions regarding the mechanism of sugar translocation by transporters of the major facilitator superfamily. In all three of these symporters, we observed sugar binding and transport in real time to determine KM, Vmax, KD, and kobs values for different sugar substrates. KD and kobs values were attainable because of a conserved sugar-induced electrogenic conformational transition within these transporters. We also analyzed interactions between the residues in the available X-ray sugar/H+ symporter structures obtained with different bound sugars. We found that different sugars induce different conformational states, possibly correlating with different charge displacements in the electrophysiological assay upon sugar binding. Finally, we found that mutations in XylE altered the kinetics of glucose binding and transport, as Q175 and L297 are necessary for uncoupling H+ and d-glucose translocation. Based on the rates for the electrogenic conformational transition upon sugar binding (>300 s−1) and for sugar translocation (2 s−1 − 30 s−1 for different substrates), we propose a multiple-step mechanism and postulate an energy profile for sugar translocation. We also suggest a mechanism by which d-glucose can act as an inhibitor for XylE. 相似文献
109.
110.
Gregor Schlüter Arzu Celik Renato Obata Mike Schlicker Sigrun Hofferbert Astrid Schlung Ibrahim M. Adham Wolfgang Engel 《Molecular reproduction and development》1996,43(1):1-6
Structural data are presented on the protamine gene cluster (PGC) of human, mouse, rat, and bull. By restriction mapping we demonstrate that the organization of the protamine cluster is conserved throughout all four species, i.e., the genes are situated in a head to tail arrangement in the order: protamine l-protamine 2-transition protein 2. Further, we established the nucleotide sequence of the entire human PGC (25 kb in total) and the 3′ portion of the rat protamine cluster (PRM2 and TNP2 genes and intergenic region). In addition, a 1 kb fragment of the bovine and murine protamine cluster, situated between PRM2 and TNP2, was sequenced. This fragment is conserved regarding sequence, position, and orientation in all species examined, and was classified as likely coding region by gene recognition program GRAIL. Using the rat fragment as a probe in RNA blots, we detected a testis-specific signal of about 0.5 kb. Finally, we demonstrate a high density of Alu elements, both full and fragmented copies, in the human PGC and discuss their localization with respect to evolutionary and functional aspects. © 1996 Wiley-Liss, Inc. 相似文献