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Journal Issue - Volume 8 Issue 12 (January 1999)

  • Acetylcholinesterase of th birthday

  • Ruth Arnon, Rebeca Tarrab‐Hazdai, Israel Silman
  • Published in Wiley Interscience on Dec 31, 2008
  • DOI: 10.1110/ps.8.12.2553 (p 2553-2561)

Abstract Acetylcholinesterase (AChE) is an enzyme broadly distributed in many species, including parasites. It occurs in multiple molecular forms that differ in their quaternary structure and mode of anchoring to the cell surface. This review summarizes biochemical and immunological investigations carried out in our laboratories on AChE of the helmint, Schistosoma mansoni. AChE appears in S. mansoni in two principal molecular forms, both...

Abstract Recent developments on virus‐like particles have demonstrated their potential in transfecting eucaryotic cells. In the case of particles based on the major coat protein VP1 of polyoma virus, transfection occurs via binding of VP1 to sialic acids. Since sialic acid is present on almost every eucaryotic cell line, this results in an unspecific cell targeting. Generation of a cell‐type specificity of this system would imply...

Abstract Protein phosphatase 1 (PP1) is widely distributed among tissues and species and acts as a regulator of many important cellular processes. By targeting the catalytic part of PP1 (PP1C) toward particular loci and substrates, regulatory subunits constitute key elements conferring specificity to the holoenzyme. Here, we report the identification of an (α/β)8‐barrel‐like structure within the N‐ter stretch of the human PP1 regulatory subunit...

Abstract Calerythrin is a 20 kDa calcium‐binding protein isolated from gram‐positive bacterium Saccharopolyspora erythraea. Based on amino acid sequence homology, it has been suggested that calerythrin belongs to the family of invertebrate sarcoplasmic EF‐hand calcium‐binding proteins (SCPs), and therefore it is expected to function as a calcium buffer. NMR spectroscopy was used to obtain structural information on the protein in solution....

Abstract The neurotrophins are growth factors that are involved in the development and survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediated through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain‐derived...

Abstract We present direct evidence for a change in protein structural specificity due to hydrophobic core packing. High resolution structural analysis of a designed core variant of ubiquitin reveals that the protein is in slow exchange between two conformations. Examination of side‐chain rotamers indicates that this dynamic response and the lower stability of the protein are coupled to greater strain and mobility in the core. The...

Abstract α1‐Microglobulin (α1m) is an electrophoretically heterogeneous plasma protein. It belongs to the lipocalin superfamily, a group of proteins with a three‐dimensional (3D) structure that forms an internal hydrophobic ligand‐binding pocket, α1m carries a covalently linked unidentified chromophore that gives the protein a characteristic brown color and extremely heterogeneous optical properties. Twenty‐one different colored tryptic...

Abstract The binding free energies of four inhibitors to bovine β‐trypsin are calculated. The inhibitors use either ornithine, lysine, or arginine to bind to the S1 specificity site. The electrostatic contribution to binding free energy is calculated by solving the finite difference Poisson‐Boltzmann equation, the contribution of nonpolar interactions is calculated using a free energy‐surface area relationship and the loss of...

Abstract Sequential 1H‐NMR assignments of mouse [Cd7]‐metallothionein‐l (MT1) have been carried out by standard homonuclear NMR methods and the use of an accordion‐heteronuclear multiple quantum correlation (HMQC) experiment for establishing the metal, 113Cd2+, to cysteine connectivities. The three‐dimensional structure was then calculated using the distance constraints from two‐dimensional nuclear Overhauser effect (NOE) spectroscopy spectra...

Abstract Pyrazole and its 4‐alkyl substituted derivatives are potent inhibitors for many alcohol dehydrogenases. However, the human σσ isoenzyme exhibits a 580‐fold lower affinity for 4‐methylpyrazole than does the human β1β1 isoenzyme, with which it shares 69% sequence identity. In this study, structural and kinetic studies were utilized in an effort to identify key structural features that affect the binding of 4‐methylpyrazole in human...

Abstract Microcalorimetry has been used to measure the stabilities of mutational variants of yeast iso‐1 cytochrome c in which F82 and L85 have been replaced by other hydrophobic amino acids. Specifically, F82 has been replaced by Y and L85 by A. The double mutant F82Y, L85A iso‐1 has also been studied, and the mutational perturbations are compared to those for the two single mutants, F82Y iso‐1 and L85A iso‐1. Results are interpreted in terms...

Abstract The crystal structure of the S642A mutant of mitochondrial aconitase (mAc) with citrate bound has been determined at 1.8 Å resolution and 100 K to capture this binding mode of substrates to the native enzyme. The 2.0 A resolution, 100 K crystal structure of the S642A mutant with isocitrate binding provides a control, showing that the Ser → Ala replacement does not alter the binding of substrates in the active site. The...

Abstract The human fibrinogen γ‐chain C‐terminal segment functions as the platelet integrin binding site as well as the Factor XIIIa cross‐linking substrate and thus plays an important role in blood clot formation and stabilization. The three‐dimensional structure of this segment has been determined using carrier protein driven crystallization. The C‐terminal segment, γ‐(398–411), was attached to a linker sequence at the C‐terminus...

Abstract We have determined the three‐dimensional structure of the potassium channel inhibitor HsTX1, using nuclear magnetic resonance and molecular modeling. This protein belongs to the scorpion short toxin family, which essentially contains potassium channel blockers of 29 to 39 amino acids and three disulfide bridges. It is highly active on voltage‐gated Kv1.3 potassium channels. Furthermore, it has the particularity to possess a...

Abstract The monoclonal antibody 1696, directed against the HIV‐1 protease, displays strong inhibitory effects toward the catalytic activity of the enzyme of both the HIV‐1 and HIV‐2 isolates. This antibody cross‐reacts with peptides that include the N‐terminus of the enzyme, a region that is well conserved in sequence among different viral strains and which, furthermore, is crucial for homodimerization to the active enzymatic form....

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