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Identification of the probable inhibitory reactive sites of the cysteine proteinase inhibitors human cystatin C and chicken cystatin
When an excess of human cystatin C or chicken cystatin was mixed with papain, an enzyme-inhibitor complex was formed immediately. The residual free cystatin was then progressively converted to a form with different electrophoretic mobility and chromatographic properties. The modified cystatins were isolated and sequenced, showing that there had been cleavage of a single peptide bond in each molecu
Preferential site occupancy observed in coexpanded argon-krypton clusters
Free heterogeneous argon-krypton clusters have been produced by coexpansion and investigated by means of x-ray photoelectron spectroscopy. By examining cluster surface and bulk binding energy shifts, relative intensities, and peak widths, we show that in the mixed argon-krypton clusters the krypton atoms favor the bulk and argon atoms are pushed to the surface. Furthermore, we show that krypton at
Asymmetric dinuclear metal complexes as models for active sites in hydrolases and redox enzymes
Site-Selective Participator Decay of Core-Excited Butadiene
The decay of core-excited electronic states in free 1,3 trans butadiene molecules has been studied using high-resolution synchrotron radiation and electron spectrometry. The core-level energy shift between the terminal and central carbon atoms is 0.64 eV making selective excitation of core electrons from these atoms possible. Resonant excitation to the au(*) valence state leads to autoionizing dec
The structures of human dihydroorotate dehydrogenase with and without inhibitor reveal conformational flexibility in the inhibitor and substrate binding sites.
Inhibitors of dihydroorotate dehydrogenase (DHODH) have been suggested for the treatment of rheumatoid arthritis, psoriasis, autoimmune diseases, Plasmodium, and bacterial and fungal infections. Here we present the structures of N-terminally truncated (residues Met30-Arg396) DHODH in complex with two inhibitors: a brequinar analogue (6) and a novel inhibitor (a fenamic acid derivative) (7), as wel
Identification of Y589 and Y599 in the juxamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2
Protein H--a surface protein of Streptococcus pyogenes with separate binding sites for IgG and albumin
Protein H, a molecule expressed at the surface of some strains of Streptococcus pyogenes, has affinity for the constant (IgGFc) region of immunoglobulin (Ig) G. In absorption experiments with human plasma, protein H-sepharose could absorb not only IgG but also albumin from plasma. The affinity constant for the reaction between albumin and protein H was 7.8 x 10(9) M-1, which is higher than the aff
4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling
A combination of access to preassociation sites and local accumulation tendency in the direct vicinity of G-N7 controls the rate of platination of single-stranded DNA
Adduct formation between cationic reagents and targets on DNA are facilitated by the ability of DNA to attract cations to its surface. The electrostatic interactions likely provide the basis for the documented preference exhibited by cisplatin and related compounds for nuclear DNA over other cellular constituents. As an extension of a previous communication, we here present an investigation illust
Hematopoietic secretory granules as vehicles for the local delivery of cytokines and soluble cytokine receptors at sites of inflammation.
Cytokines play an important role in the regulation of homeostasis and inflammation. A de-regulated cytokine function can subsequently promote chronic inflammation. This is supported by clinical evidence showing the beneficial effect of inhibiting TNF-alpha through injection of antibodies and soluble receptor in disorders such as rheumatoid arthritis and Crohn's disease. Systemic anti-TNF-alpha the
Sorting of soluble TNF-receptor for granule storage in hematopoietic cells as a principle for targeting of selected proteins to inflamed sites.
Analysis of binding sites on complement factor I that are required for its activity.
The central complement inhibitor factor I (FI) degrades activated complement factors C4b and C3b in the presence of cofactors such as C4b-binding protein, factor H, complement receptor 1 and membrane cofactor protein. FI is a serine protease composed of two chains; the light chain comprises the serine protease domain, while the heavy chain contains several domains: the FI and membrane attack compl