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PubMed1991

Some structural features of the iron-uptake regulation protein.

An extensive proton nuclear magnetic resonance study of the iron-uptake regulation protein (Fur) from Escherichia coli has been made. Considerable difficulties were experienced in the NMR experiments in 1H2O which may be due unfavourable proton exchange rates in the pH range greater than 6.2, where the protein is soluble. Even in 2H2O, the two-dimensional NMR spectra were not easily interpreted due to widely differing line widths, as a result of the protein side-chains having very differing mobilities. Despite these problems, virtually all the 20 aromatic amino acids have been assigned. Small regions of the protein core were assigned by taking advantage of the approximately 20 non-exchanging peptide-NH resonances in 2H2O. Using two-dimensional J-correlated, homonuclear Hartmann-Hahn and NOE spectroscopies, we have been able to give some assignments in which there is considerable confidence for about one third of the amino acids. Taking advantages of two series of probe experiments, using Mn(II) and a spin label, together with longer range NOE data and result from structure predictions and CD data, we have put forward a tentative fold for the protein which is seen to have a relatively rigid series of interior strands and more flexible exterior strands, many of which are likely to be helical. The Mn(II) probe experiments have also allowed us to define the Fe(II) binding site.

Amino Acid Sequence↗

PubMed1989

Recombinant TGF-beta 1 is synthesized as a two-component latent complex that shares some structural features with the native platelet latent TGF-beta 1 complex.

The entire coding region of the human transforming growth factor beta 1 (TGF-beta 1) precursor cDNA has been stably expressed in a human renal carcinoma cell line. Like platelet TGF-beta 1, the recombinant TGF-beta 1 is secreted in a biologically latent form. Immunoblot analysis and gel-filtration indicate that the recombinant latent TGF-beta 1 is a 100-kDa complex in which active 25-kDa TGF-beta 1 is noncovalently associated with the remaining 75 kDa of the processed precursor. Unlike the platelet latent complex, the recombinant latent complex contains no 135-kDa component. Thus, the processed precursor peptide alone is sufficient to confer latency on active TGF-beta 1, and the 135-kDa platelet component has a different role. The processed precursor is similarly glycosylated in recombinant and platelet complexes, and in both has an exposed heparin binding site that may be involved in targeting of the latent complex. Finally, acid activation of recombinant and platelet complexes is reversible, suggesting that the activation process does not cause major structural modifications in the components of the latent complex.

Binding Sites↗

PubMed1990

Characterization and comparative structural features of the gene for human interstitial retinol-binding protein.

We have cloned the gene for human interstitial retinol-binding protein (IRBP) and compared its nucleotide sequence with that of the corresponding cloned cDNA. The human IRBP gene is approximately 9.5 kilobase pairs (kbp) in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da. The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively. This unusual structure is shared with the bovine IRBP gene. A large (1.7 kbp) fragment appears to have been lost from the 3'-noncoding region of the last human exon. We conclude that the human and bovine genes have similar evolutionary histories.

Amino Acid Sequence↗

PubMed1997

Structural features of Glycera dibranchiata monomer hemoglobins. Primary sequences of monomer hemoglobin components II and III.

Primary sequences for the remaining two members (GMH2, GMH3) of the group of three major monomeric hemoglobins from the marine annelid Glycera dibranchiata have been obtained. Full sequences of each 147-amino acid globin were achieved with a high degree of confidence using standard Edman technology in combination with molecular mass determinations of the intact globins and of the cyanogen bromide cleavage fragments using electrospray ionization mass spectrometry. When minor assumptions concerning Q/E identities are made these new results indicate the likely correspondence of GMG2 with the protein represented by the first Glycera dibranchiata monomer hemoglobin complete sequence [Imamura et al., (1972), J. Biol. Chem. 247, 2785-2797]. When these new sequences are combined with the previously determined primary sequence for the third major monomer hemoglobin, GMH4 [Alam et al., J. Protein Chem. (1994), 13, 151-164], it becomes clear that these three (GMG2-4) are truly distinct proteins, contrary to previous suggestions. Surprisingly, our results show that none of these three primary sequences is identical to the published sequence of the refined monomer hemoglobin crystal structure protein; however, there is a strong correspondence to the GMG2 sequence. The present sequencing results, in combination with the published GMH4 sequence, confirm the presence of a distal Leu in place of the more commonly encountered distal His in all three of the major monomer hemoglobins isolated in this laboratory and indicate that the unusual B10 Phe occurs only in GMH4. Analysis of the sequences presented here, along with comparison of amino acid content for Glycera dibranchiata monomer hemoglobins isolated from three different laboratories, and comparison of NMR results from two laboratories suggest further correspondence which unify disparate published isolations.

Amino Acid Sequence↗

PubMed1989

Bent DNA is a structural feature of scaffold-attached regions in Drosophila melanogaster interphase nuclei.

In this study the SAR DNA (scaffold attached region DNA) of some Drosophila genes was analyzed. Bent DNA regions were found to be present in all SAR DNA fragments analyzed here. Bent non-SAR DNA exhibits SAR-like properties when it is exogenously added to lithium 3,5-di-iodosalicylate-extracted Drosophila nuclear scaffolds. Thus the presence of bent regions within SAR DNA fragments might be a prerequisite for the SAR-like behavior of a DNA fragment.

Animals↗

PubMed1989

Structural features of CD4 required for binding to HIV.

A soluble form of the human CD4 glycoprotein (sCD4), the cellular receptor for human HIV, was treated with various physical, chemical, and enzymic regimens and tested over a range of concentrations for its capacity to inhibit the binding of HIV to CD4+ T cells. Reduction of disulfide bonds and alkylation in denaturing buffer (8 M urea) destroyed the inhibitory activity of sCD4, whereas reduction and alkylation in PBS had no effect. Derivatization or digestion of carbohydrate groups by periodate oxidation or by glycolytic enzyme digestion did not affect sCD4 inhibitory capacity. Digestion with trypsin or endoproteinase Glu-C destroyed activity. A limited digestion of sCD4 with endoproteinase Glu-C resulted in a mixture of fragments, however, and the mixture had inhibitory activity equivalent to that of intact sCD4. Within this mixture, a fragment of 23 kDa was identified that binds to HIV. Although sCD4 can be digested to yield fully active fragments, the requirement for intrachain disulfide bonding indicates that the minimum sized portion of CD4 that will retain full affinity for HIV will have to be formulated with a proper tertiary structure.

Antigens, Differentiation, T-Lymphocyte↗

PubMed2002

Nitric oxide formation and corresponding relaxation of porcine coronary arteries induced by plant phenols: essential structural features.

The high intake of polyphenols is thought to contribute to the beneficial cardiovascular effects of plant-centered diets. A putative mechanism underlying the cardioprotective activity is thought to be a plant phenol-induced increase of nitric oxide formation by the constitutive endothelial nitric oxide synthase. Twenty-eight phenols of different classes commonly occurring in plant foods were examined for their capability of enhancing the endothelial nitric oxide release of isolated porcine coronary arteries by direct real-time measurement of the luminal surface nitric oxide concentration with an amperometric microsensor. Additionally, the relaxing activity of the phenols was measured on porcine coronary rings. Quercetin, myricetin, leucocyanidol, and oligomeric proanthocyanidins induced the highest increases in nitric oxide release (delta[NO] > 8.5 nM ); caffeic acid, fisetin, hyperosid, and isoquercitrin were moderately active (5 nM < delta[NO] < 8.5 nM ); the other phenolic compounds caused only marginal increases of the nitric oxide levels (delta[NO] < 5 nM). The nitric oxide-stimulating activity of the phenols was uniformly positively correlated with their vasorelaxing activity. However, endothelium-dependent vasorelaxations were limited to phenols inducing nitric oxide elevations > 5 nM (= Km value of the soluble guanylate cyclase). Analysis of structure-activity relations revealed that a high nitric oxide activity was confined to a flavan-moiety with free hydroxyl-residues at C3, C3', C4', C5, and C7 and a hydroxyl-, oxo-, or phenolic substituent at C4, whereas the caffeic acid scaffolding emerged as the minimally essential motif for the nitric oxide-dependent vasorelaxation.

Animals↗

PubMed1996

Chemistry of Bis(aryloxo)palladium(II) Complexes with N-Donor Ligands: Structural Features of the Palladium-to-Oxygen Bond and Formation of O-H.O Bonds.

Reaction of palladium acetate with 2 equiv of sodium phenoxide in the presence of a chelate diamine ligand affords the complexes [Pd(OPh)(2)(N approximately N)] (N approximately N = bpy (1), tmeda (2), teeda (3), dpe (4), dmap (5)). These yellow to orange bis(phenoxo)palladium(II) complexes are thermally stable at room temperature in the solid state as well as in solution. Addition of an excess of pentafluorophenol to 1, 2, 4, and 5 affords crystalline complexes [Pd(OC(6)F(5))(2)(N approximately N)] (N approximately N = bpy (6), tmeda (7), dpe (8), dmap (9)). Crystals of 1 and 6 have been subjected to X-ray diffraction studies. Crystals of 1 are orthorhombic, space group P2(1)2(1)2(1) (no. 19), with a = 6.7655(6) Å, b = 16.0585(10) Å, c = 16.7275(13) Å, and Z = 4. Crystals of 6 are triclinic, space group P&onemacr; (no. 2), with a = 7.567(4) Å, b = 12.708(3) Å, c = 12.912(5) Å, alpha = 61.51(3) degrees, beta = 74.74(4) degrees, gamma = 88.78(4) degrees, and Z = 2. The molecular structures of 1 and 6 show them to be square-planar complexes, and the main structural difference between these complexes is the orientation of the aromatic rings. In 6 the OC(6)F(5) ligands are almost parallel in a face-to-face orientation (pi-pi stacking interactions), whereas in 1 the OC(6)H(5) units are skewed away from each other. An unexpected "mixed" alkoxo(aryloxo) complex [Pd(OCH(CF(3))(2))(OPh)(bpy)].HOPh (10) is formed when 1 is reacted with 1,1,1,3,3,3-hexafluoro-2-propanol. The molecular structure of 10 shows O-H.O hydrogen bonding (O.O = 2.642(8) Å) between the hydroxyl hydrogen of phenol and the oxygen atom of the phenoxide ligand as well as an additional C-H.O contact (C.O) = 2.95(1) Å), which can be regarded as the initial stage of a base-assisted beta-hydrogen elimination. Crystals of 10 are monoclinic, space group P2(1)/c, with a = 8.3241(14) Å, b = 11.0316(17) Å, c = 26.376(3) Å, alpha = 93.01(1) degrees, Z = 4. Spectroscopic data of complexes 1-10 indicate that the oxygen atom of the aryloxide or alkoxide ligand is extremely electron-rich, leading to high polarization of the palladium-to-oxygen bond. The bis(phenoxide) complexes 1, 2, and 4 associate with two molecules of phenol through O-H.O hydrogen bonds to form adducts [Pd(OPh)(2)(N approximately N)].2HOPh (N approximately N = bpy (11), tmeda (12), dpe (13)). The palladium complexes 6-9 with OC(6)F(5) groups show no tendency to form adducts with alcohols.

Journal Article↗

PubMed1988

Somatostatin-related and glucagon-related peptides with unusual structural features from the European eel (Anguilla anguilla).

Peptides derived from prosomatostatins I and II and from two distinct proglucagons have been isolated from the pancreas of a teleost fish, the European eel (Anguilla anguilla). The product of prosomatostatin I processing, somatostatin-14, is identical to mammalian somatostatin-14. A 25-amino-acid-residue peptide (Ser-Val-Asp-Asn-Gln5-Gln-Gly-Arg-Glu-Arg10-Lys-Ala-Gly-Cys- Lys15-Asn-Phe-Tyr- Trp-Lys20-Gly-Pro-Thr-Ser-Cys25) is derived from prosomatostatin II. Compared with the corresponding peptides from other teleost fish, the eel somatostatin-25 contains the unusual substitution Pro for Phe at position 22. This peptide was also isolated in a form containing a hydroxylsyl residue at position 20. A 29-amino-acid-residue eel glucagon contains four substitutions relative to human glucagon Asn for Ser8, Glu for Asp15, Thr for Ser16, and Ser for Thr29). In common with mammalian and avian glucagons but unlike most other fish glucagons, the eel peptide possesses a glutamine residue at position 3. A peptide derived from a second proglucagon comprises 36 amino acid residues. A 7-residue C-terminal extension to the glucagon sequence shows structural similarity to the corresponding extension in ratfish (Hydrolagus colliei) glucagon and mammalian oxyntomodulin.

Amino Acid Sequence↗

PubMed1993

The effects of cobalt-hexammine and cobalt-pentammine cations on the solution structure of calf-thymus DNA. DNA condensation and structural features studied by FTIR difference spectroscopy.

The interaction of calf-thymus DNA with cobalt-hexammine and cobalt-pentammine cations was investigated, in aqueous solution at pH 6-7 with cation/DNA(phosphate) molar ratios r = 1/80, 1/40, 1/20, 1/10, 1/4, 1/2 and 1, using Fourier Transform infrared (FTIR) difference spectroscopy. Correlations between spectral changes, DNA condensation and helical stabilization due to the cation interaction as well as conformational features are established. At a very low cation concentration (r = 1/80), the binding of cobalt-hexammine cation with DNA is through the H-bond formation between cation NH3 groups and the PO2 groups of the backbone, resulting in duplex stability. As the cation concentration increases, hydrogen bonding expands towards guanine N-7 and O-6 atoms. At r > 1/20, DNA condensation occurs with major reduction in the intensity of several DNA in-plane vibrations and that of the phosphate group. The cobalt-pentammine cation binding is via the PO2 groups (directly) at very low metal cation concentration (r = 1/80) and the guanine N-7 and the O-6 groups (indirectly) at higher ratios. At r > 1/10, DNA condensation begins with some degree of direct cation-base binding. No major conformational changes from the B-family structure were observed before and after DNA collapse, in the presence of cobalt-ammine cations.

Animals↗

PubMed2002

FCRL, a novel member of the leukocyte Fc receptor family possesses unique structural features.

A novel conserved member of the leukocyte Fc receptor (FcR) family was identified in human and mouse. The presumably secreted protein, designated FCRL (FcR-like) is comprised of four domains. The three N-terminal domains are related to the extracellular region of FcgammaRI, with the second (35-37% residue identity) and the third (46-52%) domains showing highest similarity. The C-terminal domain is a unique sequence enriched with proline residues. In humans, alternative transcripts for six FCRL isoforms were revealed. Spleen and tonsils were found to be the major sources of FCRL mRNA in human tissues. Western blotting of tonsil cell lysate using FCRL-specific antibodies recognized a 44-kDa protein produced as a monomer containing free sulfhydryl groups. The monomer, however, was able to form disulfide-linked homo-oligomer upon oxidation. In COS-7 cells transiently transfected with two human FCRL isoforms, both resided intracellularly. Immunohistochemical staining of tonsil sections demonstrated the FCRL expression in germinal centers, suggesting that the protein may be implicated in germinal center-specific stages of B cell development. The phylogenetic analysis of the FCRL relationships with the leukocyte FcR supports a view that the three-domain structure was primordial in the evolution of the family.

Alternative Splicing↗

PubMed2004

Structural features of transcription factor IIIA bound to a nucleosome in solution.

Assembly of a DNA fragment containing a Xenopus borealis somatic-type 5S RNA gene into a nucleosome greatly restricts binding of the 5S gene-specific transcription factor IIIA (TFIIIA) to the 5S internal promoter. However, TFIIIA binds with high affinity to 5S nucleosomes lacking the N-terminal tail domains of the core histones or to nucleosomes in which these domains are hyperacetylated. The degree to which tail acetylation or removal improves TFIIIA binding cannot be simply explained by a commensurate change in the general accessibility of nucleosomal DNA. In order to investigate the molecular basis of how TFIIIA binds to the nucleosome and to ascertain if binding involves all nine zinc fingers and/or displacement of histone-DNA interactions, we examined the TFIIIA-nucleosome complex by hydroxyl radical footprinting and site-directed protein-DNA cross-linking. Our data reveal that the first six fingers of TFIIIA bind and displace approximately 20 bp of histone-DNA interactions at the periphery of the nucleosome, while binding of fingers 7 to 9 appears to overlap with histone-DNA interactions. Molecular modeling based on these results and the crystal structures of a nucleosome core and a TFIIIA-DNA cocomplex yields a precise picture of the ternary complex and a potentially important intermediate in the transition from naïve chromatin structure to productive polymerase III transcription complex.

Animals↗

PubMed1982

Structural features of liver microsomal NADPH-cytochrome P-450 reductase. Hydrophobic domain, hydrophilic domain, and connecting region.

Detergent-solubilized liver microsomal NADPH-cytochrome P-450 reductase is known to retain the ability to transfer electrons to cytochrome P-450, whereas the trypsin-solubilized reductase transfers electrons only to artificial acceptors. Due to the loss of a hydrophobic fragment by the action of trypsin, the altered reductase is no longer capable of binding cytochrome P-450. In the present study the primary tryptic attack on the rabbit reductase was shown to be at the Lys 44-Ile 45 bond to liberate the hydrophilic domain (molecular weight, 71,000) from the intact enzyme (molecular weight, 77,000). The other fragment (molecular weight, 4,800) undergoes tryptic attack at the Lys 34-Lys 35-Lys 36 sequence to yield a polypeptide representing the hydrophobic domain of the reductase and a nona- or decapeptide (Lys 35 or Lys 36 through Lys 44) which serves as the connecting region. The hydrophobic peptide, which is derived from the NH2-terminal end of the reductase, has an acetylated NH2 terminus and a region (Val 16 through Phe 32) which is exceptionally hydrophobic, with a predicted beta-sheet structure, and is believed to be involved in the binding of cytochrome P-450 and phospholipid. The site of attack on the reductase by various proteases is different, but the cleavage points are localized within a short segment of the polypeptide chain. A comparison of the tryptic forms (representing the hydrophilic domains) of the rabbit and rat reductases by terminal sequence analysis showed a high degree of similarity, with about 80% of the residues in exact correspondence and only a short variable region near the Ile NH2 terminus.

Amino Acid Sequence↗

PubMed1987

Structural features of the terminal loop region of frog retinal rod outer segment disk membranes: II. Organization of the terminal loop complex.

In addition to a lipid bilayer component (Corless, Fetter, and Costello: J. Comp. Neurol. 257:1-8, '87), the terminal loop region of frog rod outer segment (ROS) disks displays a clustering of discrete elements referred to as the terminal loop complex. It consists of (1) semicircular or crescentic densities within the terminal loop, (2) linear interdisk densities spanning the cytoplasm near terminal loops, and (3) distinctive freeze-fracture particles associated with the terminal loop, located between 1 and 2. The linear interdisk densities are organized on a two-dimensional lattice that appears to ensheath completely the lamellar domains of all ROS disks. Indirect evidence is presented for a net axial alignment of intraloop densities. We interpret the large freeze-fracture particles of the terminal loop region to reflect transmembrane components that connect the interdisk and intraloop densities. Thus, we propose that the entire terminal loop (TL) complex is organized on a two-dimensional net. We further infer that each TL complex is organized as a dimeric unit and that such dimers interact axially and laterally to generate the observed lattice structure. It is suggested that one component of the terminal loop complex is the high molecular weight protein localized along the disk perimeter by Papermaster, Schneider, Zorn, and Kraehenbuhl (J. Cell. Biol. 78:415-425, '78).

Animals↗

PubMed2001

Modification of cell response to insulin by membrane-acting agents in rat white adipocytes: analysis of structural features by computational simulation.

The effect of membrane-acting agents, biscoclaurine alkaloids (cepharanthine, tetrandrine, isotetrandrine), carbobenzoxy-D-Phe-L-Phe-Gly (z-FFG), and tyrphostin AG17, on the insulin-involved fatty acid synthesis by an beta-agonist (e.g., isoproterenol) in adipocytes was examined. The alkaloids dose-dependently enhanced the insulin-involved fatty acid synthesis in rat white adipocytes, stabilized the C(6)-NBD-PC (1-acyl-2-[6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-caproyl]-sn-glycero-3-phosphatidylcholine) model membrane, and suppressed the phospholipase A(2)-induced phospholipid degradation. In contrast, z-FFG had no effect on the fatty acid synthesis or the membrane stability. Tyrphostin AG17 suppressed insulin action, but promoted the model membrane stabilization. In the same culture conditions as for the fatty acid synthesis assay, cepharanthine, z-FFG and tyrphostin AG17 had no effect on the transcript levels of glucose transporter isoforms (GLUT 1, 4) and hexokinase isozymes (HK I, II) in rat white adipocytes. Thus, these membrane-acting agents modify the insulin action via a change in the cell membrane condition, and do not directly act on the insulin-involved glucose metabolism. Then we analyzed the structural conformation of these membrane-acting agents by computational simulations. The alkaloids had an elliptic macrocyclic structure, and the order of ellipticity (cepharanthine>tetrandrine>isotetrandrine) agreed with that of the modifying ability for insulin action. The distribution of electrostatic potential fields of these alkaloids was essentially equal by turn in surrounding with the dipole moments. Both in z-FFG and tyrphostin AG17, the distribution pattern of electrostatic potential fields was different from that of the alkaloids. Judging from these results, we concluded that the electrostatic potential field is a good index of the modification of insulin action, and the elliptic structure in these alkaloids is regarded with the modification of insulin action.

Adipocytes↗

PubMed2003

Collagen XXIV, a vertebrate fibrillar collagen with structural features of invertebrate collagens: selective expression in developing cornea and bone.

Tissue-specific assembly of fibers composed of the major collagen types I and II depends in part on the formation of heterotypic fibrils, using the quantitatively minor collagens V and XI. Here we report the identification of a new fibrillar-like collagen chain that is related to the fibrillar alpha1(V), alpha1(XI), and alpha2(XI) collagen polypeptides and which is coexpressed with type I collagen in the developing bone and eye. The new collagen was designated the alpha1(XXIV) chain and consists of a long triple helical domain flanked by typical propeptide-like sequences. The carboxyl propeptide is classic, with 8 conserved cysteine residues. The amino-terminal peptide contains a thrombospodin-N-terminal-like (TSP) motif and a highly charged segment interspersed with several tyrosine residues, like the fibril diameter-regulating collagen chains alpha1(V) and alpha1(XI). However, a short imperfection in the triple helix makes alpha1(XXIV) unique from other chains of the vertebrate fibrillar collagen family. The triple helical interruption and additional select features in both terminal peptides are common to the fibrillar chains of invertebrate organisms. Based on these data, we propose that collagen XXIV is an ancient molecule that may contribute to the regulation of type I collagen fibrillogenesis at specific anatomical locations during fetal development.

Amino Acid Motifs↗

PubMed1997

Oxidized and phosphorylated synthetic peptides corresponding to the second and third tubulin-binding repeats of the tau protein reveal structural features of paired helical filament assembly.

The microtubule-associated protein tau of normal brains is attached to tubulin through its 18-amino-acid repeat units. In the paired helical filaments (PHF) of Alzheimer's disease, however, tau is oligomerized in an abnormally hyperphosphorylated from (PHF-tau). tau contains two cysteine residues in repeat units 2 and 3, but only the R3-R3 homodimer is present in PHF-tau. A serine residue two amino acids downstream of the R3 cysteine is a major phosphate acceptor site for protein kinase C. In the work repeated here, we used synthetic peptides corresponding to R2, R3 and phosphorylated R3 to determine the binding of the tau repeat peptides to a peptide fragment corresponding to the C-terminal domain of beta-tubulin and to study the kinetics of homo- and heterodimer formation. Additionally, we studied two major biochemical properties of the peptides that distinguish between normal tau and PHF-tau: conformation and metabolic stability. All R2 and R3 peptides bound specifically to the tubulin peptide regardless of the state of phosphorylation or dimerization. The reverse-turn conformation of the tau repeat peptides in the presence of the tubulin peptide remained unaffected. Phosphorylation slightly loosened the turn structure of the monomeric and dimeric peptides, and did not univocally affect the serum stability of the peptides or the ability of the peptides to form dimers. The isolated R2 and R3 units formed homodimers approximately in the same rate. When the two peptides were mixed, however, the R2-R3 heterodimer was formed preferentially over the homodimers. The dimers were generally more stable in human serum than the monomers. Our results with the synthetic peptide fragments of tau indicate that neither oxidation nor phosphorylation of the repeat units is able to generate extended structure such as that found in PHF-tau. Additionally, phosphorylation of Ser324 does not appear to modulate the kinetics of oligomerization of tau, and in general biochemistry terms, does not affect disulfide bridge formation nearby. In agreement with studies at the full-protein level, the formation of homodimers of the peptides, a model of the self-association of tau, is not preferred. If the dimers are formed, however, their clearance is considerably slower than that of the monomers, explaining the remarkable protease resistance of PHF-tau in the affected brains.

Alzheimer Disease↗

PubMed1982

Structural features of cytochalasins responsible for gram-positive bacterial inhibitions.

A study of the relative effectiveness of some eighteen natural and synthetically modified cytochalasins on the uptake of glucose by the Gram-positive bacterium Arthrobacter sialophilus showed that cytochalasins B, C or D and aspochalasins A, C or D were inactive natural congeners. The presence of an alpha,beta-unsaturated carbonyl group in the macrolide moiety of these compounds with appropriate bioisosteric placement, as exemplified by cytochalasin A and aspochalasin B, are requisite molecular features. The transmembrane inhibitory index of active compounds was enhanced by increasing their lipophilicity. Thiol adducts of CA were around 20% as active in solute uptake inhibition as was the free drug. Radioactive 7-O-acetyl CA and its thiol adduct were each rapidly taken up by A. sialophilus and remained firmly bound to cellular components even after denaturant manipulations. These findings provide strong evidence for a stable association between CA and presumptive macromolecular receptors in transport and related processes.

Arthrobacter↗