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61.
S100A6, a calcium-binding protein also known as calcyclin, was detected in human umbilical cord by immunoblotting. Immunohistochemical studies showed an intensive reaction for S100A6 in the walls of vessels and Wharton's jelly. In the latter, S100A6 was found not only in the myofibroblasts but also in the ECM (extracellular matrix) surrounding these cells. Affinity chromatography of S100A6 resin indicated that Wharton's jelly contains some proteins that could bind to S100A6. Thus these novel results show the presence of S100A6 in umbilical cord and suggest the involvement of this protein in intra- and extra-cellular signalling pathways in this tissue. 相似文献
62.
Handzlik J Szymańska E Wójcik R Dela A Jastrzębska-Więsek M Karolak-Wojciechowska J Fruziński A Siwek A Filipek B Kieć-Kononowicz K 《Bioorganic & medicinal chemistry》2012,20(14):4245-4257
The study is focused on a series of 5-arylidenehydantoin derivatives with a phenylpiperazine-hydroxypropyl fragment at N3 of the hydantoin ring. The compounds were assessed on their affinity for α(1)-adrenoceptors and evaluated in functional bioassays for their antagonistic properties. Crystal structures of (Z)-5-(4-chlorobenzylidene)-3-(3-(4-(2-ethoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)imidazolidine-2,4-dione (7) and hydrochloride of (Z)-5-(4-chlorobenzylidene)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (10a) were solved using the X-ray diffraction method. Classical molecular mechanics (MMFFs force field, MCMM, MacroModel) were used to predict 3D structure of compounds 5a-18a using a crystal structure of 7. SAR analysis was performed on the basis of Barbaro's pharmacophore model and structural properties of previously investigated α(1)-adrenoceptor antagonists possessing a hydantoin fragment. Most of the compounds exhibited significant affinities for α(1)-ARs in nanomolar range (40-290 nM). The highest activities (K(i)<75 nM) were observed for compounds possessing a 2-alkoxyphenylpiperazine fragment and two methoxy substituents at the benzylidene moiety. The results indicated that chemical properties, number and positions of substituents at the 5-arylidene fragment influenced the power of α(1)-affinities as follows: 3,4-di CH(3)O>2,4-di CH(3)O>4-Cl>2,3-di CH(3)O>H>4-N(CH(3))(2). 相似文献
63.
Caswell CC Barczyk M Keene DR Lukomska E Gullberg DE Lukomski S 《The Journal of biological chemistry》2008,283(52):36168-36175
Many pathogenic bacteria interact with human integrins to enter host cells and to augment host colonization. Group A Streptococcus (GAS) employs molecular mimicry by direct interactions between the cell surface streptococcal collagen-like protein-1 (Scl1) and the human collagen receptor, integrin alpha2beta1. The collagen-like (CL) region of the Scl1 protein mediates integrin-binding, although, the integrin binding motif was not defined. Here, we used molecular cloning and site-directed mutagenesis to identify the GLPGER sequence as the alpha2beta1 and the alpha11beta1 binding motif. Electron microscopy experiments mapped binding sites of the recombinant alpha2-integrin-inserted domain to the GLPGER motif of the recombinant Scl (rScl) protein. rScl proteins and a synthetic peptide harboring the GLPGER motif mediated the attachment of C2C12-alpha2+myoblasts expressing the alpha2beta1 integrin as the sole collagen receptor. The C2C12-alpha11+myoblasts expressing the alpha11beta1 integrin also attached to GLPGER-harboring rScl proteins. Furthermore, the C2C12-alpha11+cells attached to rScl1 more efficiently than C2C12-alpha2+cells, suggesting that the alpha11beta1 integrin may have a higher binding affinity for the GLPGER sequence. Human endothelial cells and dermal fibroblasts adhered to rScl proteins, indicating that multiple cell types may recognize and bind the Scl proteins via their collagen receptors. This work is a stepping stone toward defining the utilization of collagen receptors by microbial collagen-like proteins that are expressed by pathogenic bacteria. 相似文献
64.
Caswell CC Han R Hovis KM Ciborowski P Keene DR Marconi RT Lukomski S 《Molecular microbiology》2008,67(3):584-596
Non-specific activation of the complement system is regulated by the plasma glycoprotein factor H (FH). Bacteria can avoid complement-mediated opsonization and phagocytosis through acquiring FH to the cell surface. Here, we characterize an interaction between the streptococcal collagen-like protein Scl1.6 of M6-type group A Streptococcus (GAS) and FH. Using affinity chromatography with immobilized recombinant Scl1.6 protein, we co-eluted human plasma proteins with molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the 155 kDa band as FH and two other bands as isoforms of the FH-related protein-1. The identities of all three bands were confirmed by Western immunoblotting with specific antibodies. Structure-function relation studies determined that the globular domain of the Scl1.6 variant specifically binds FH while fused to collagenous tails of various lengths. This binding is not restricted to Scl1.6 as the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses demonstrated the cofactor activity of the rScl1.6-bound FH for factor I-mediated cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the cell wall material obtained from M6-type GAS. In conclusion, we have identified a functional interaction between Scl1 and plasma FH, which may contribute to GAS evasion of complement-mediated opsonization and phagocytosis. 相似文献
65.
Conformational preferences of a group of hexapeptides containing two dehydroamino acid residues in Positions 2 and 5 in peptide chain were investigated by means of spectroscopic methods (NMR and CD) and theoretical calculations. In the case of dimethylsulfoxide (DMSO) solution, only peptide with free N-termini adopted rigid 3(10)-helical conformation, for the rest of examined peptides extended and "zig-zag" conformers were predominant. CD measurements showed that only in chloroform solution the conformational freedom of investigated peptides was restricted. 相似文献
66.
Catherine L. Scott Slawomir Kwasniewski Stig Falk-Petersen John R. Sargent 《Polar Biology》2002,25(1):65-71
The small, sub-ice copepod Jaschnovia brevis is rich in triacylglycerols, suggesting a feeding behaviour not constrained to the seasonal phytoplankton bloom. The copepod's triacylglycerol reserves contain: the diatom biomarkers 16:1n-7 (23.9%), 20:5n-3 (8.5%) and C16 PUFA (1.3%), the flagellate biomarkers 18:4n-3 (3.7%) and 22:6n-3 (3.3%), and the Calanus copepod biomarkers 20:1n-9 (7.7%) and 22:1n-11 (6.2%). Total lipid from particulates in the water column contained polar lipid (45.0%), wax esters (24.9%) and triacylglycerols (11.2%) as major components. The total lipids in the particulates were rich in 18:1n-9 (31.5%) and 16:0 (21.2%), and relatively rich in 18:0 (7.8%) and 18:2n-6 (9.2%). The triacylglycerols in the particulates contained 16:1n-7 (20.7%), C16 PUFA (4.1%), 18:4n-3 (1.9%), 20:5n-3 (3.6%), 22:6n-3 (1.9%), 20:1n-9 (5.2%) and 22:1n-11 (3.9%). The polar lipids in the particulates contained 16:1n-7 (17.3%), C16 PUFA (7.8%), 18:4n-3 (3.3%), 20:5n-3 (14.5%) and 22:6n-3 (9.6%). The fatty alcohols in the wax esters of the particulates were mainly 16:0 (11.3%), 20:1n-9 (21.1%) and 22:1n-11 (30.6%). The nature of the particulates, their possible origin in living and non-living material, and their role in the nutrition of J. brevis are discussed. 相似文献
67.
68.
M. Kubacka N. Szkaradek S. Mogilski K. Pańczyk A. Siwek A. Gryboś B. Filipek P. Żmudzki H. Marona A.M. Waszkielewicz 《Bioorganic & medicinal chemistry》2018,26(13):3773-3784
A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α1-(compound 2 and 8), β-(compounds 1, 3, 4, 7), α1/β-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives. 相似文献
69.
Fluorescence and phosphorescence measurements have been carried out on single-p tryptophan (Trp 43 or Trp 75)-containing mutants of Tet repressor (Tet R). Tet R containing Trp 43, the residue localized in the DNA recognition helix of the repressor, has been used to observe the binding of Tet R to two 20-bp DNA sequences of tet O1 and tet O2 operators. Binding of Tet R to tet O1 operator leads to a 78% decrease of the repressor fluorescence intensity, with an accompanying 20-nm blue shift of its fluorescence emission maximum to 330 nm. Upon binding of Tet R to tet O2 operator, the Trp 43 fluorescence intensity is quenched by 60%, and a 10-nm shift of its emission maximum to 340 nm occurs. Solute fluorescence quenching studies, using acrylamide, performed at low ionic strength indicate that in both the complex of Tet R with the O1 and that with the O2 operator, Trp 43 is moderately buried, as indicated by a bimolecular rate quenching constant of about 1.8 × 109 M–1 sec–1. In contrast to the Tet R–tet O2 complex, the Stern–Volmer acrylamide quenching constant K
sv of the complex with tet O1 operator changes from 7.5 M–1 at 5 mM NaCl to 22 M–1 at 200 mM NaCl, indicating different exposures of Trp 43 in the two complexes in solutions of higher ionic strength. Phosphorescence studies showed a 0–0 vibronic transition at 408 and 403 nm for Trp 43 and Trp 75, respectively. Upon binding of Tet R to the tet operators, we observed red shifts of 0–0 vibronic bands of Trp 43 to 413 and 412 nm for tet O1 and tet O2 operator, respectively, and the phosphorescence triplet lifetime of Trp 43 at 75 K was quenched from 6.0–5.5 to 3.5–3.3 sec. The thermal phosphorescence quenching profile ranged from –200°C to –20°C, and differed drastically for the two complexes, suggesting different dynamics of the microenvironment of the Trp 43 residue. The luminescence data for Trp 43 of Tet R suggest that the recognition helix of Tet R interacts in different fashions with the tet O1 and tet O2 operators. 相似文献
70.
Eukaryotic protein‐coding genes are typically classified into two groups: those with expression regulated by specific signals versus the relatively constant “housekeeping” genes. Although these differences are associated with alternative modes of RNA polymerase II (RNAP II) pre‐initiation complex (PIC) assembly, a role for gene‐specific activators in controlling “regulatability” has been difficult to rule out. To address this question, de Jonge et al ( 2017 ) studied a group of genes controlled by a common activator but dependent on either TFIID or SAGA and found that the magnitude of regulation strongly correlates with the mechanism of PIC assembly. 相似文献