Abstract
Several small molecule inhibitors of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease have advanced successfully to clinical trials. However, the selection of drug-resistant mutants is a significant issue with protease inhibitors (PIs). A variety of amino acid substitutions in the...
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PMID: 21056040
PDF is available here.
Kiyotaka Nakano,
Takahiro Ishiguro,
Hiroko Konishi,
Megumi Tanaka,
Masamichi Sugimoto,
Izumi Sugo,
Tomoyuki Igawa,
Hiroyuki Tsunoda,
Yasuko Kinoshita,
Kiyoshi Habu,
Tetsuro Orita,
Masayuki Tsuchiya,
Kunihiro Hattori and
Hisafumi Yamada-Okabe
Abstract
We generated a humanized GC33 from complementarity-determining region grafting with the aid of both the hybrid variable region and two-step design methods. The humanized antibody bound to GPC3 specifically and induced antibody-dependent cellular cytotoxicity as effectively as a chimeric GC33 antibod...
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PMID: 20847643
PDF is available here.
Abstract
We performed mutational analysis. Mutant AHs were subjected to enzyme-linked immunosorbent assay testing for gp120-binding activity and to syncytium formation assay. As a result, it was revealed that Asp15, Tyr23, Leu25, Asn28 and Tyr32 in segment 1, Tyr61 in segment 2 and Tyr99 in segment 3 are ess...
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PMID: 20842142
PDF is available here.
Abstract
We report, by systematic mutagenesis studies, the identification of E535 as part of this Ca(2+) binding site. This site is specific for binding to Ca(2+) but not Cd(2+). Experimental results and molecular modeling based on the X-ray crystallographic structures of the BK channel cytosolic domain sugg...
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PMID: 20937866
PDF is available here.
Abstract
We show here by time-resolved optical and FTIR spectroscopy combined with time-resolved electrometry that some mutant enzymes incapable of proton pumping nevertheless initiate catalysis by proton transfer to a proton-loading site. A conserved tyrosine in the so-called D-channel is identified as a po...
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PMID: 20937896
PDF is available here.
Abstract
We engineered a series of mutant CaMs designed to individually increase the Ca²(+) affinity of each of CaM's EF-hands by increasing the number of acidic residues in Ca²(+)-chelating positions. Domain-specific Ca²(+) affinities of each CaM variant were determined by equilibrium fluorescence titrat...
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PMID: 20815817
PDF is available here.
Abstract
We report on the properties of a series of site-directed mutants of two adjacent tyrosine residues involved in iron co-ordination, and demonstrate that, in contrast with mutation of equivalent residues in the N-lobe of human transferrin, the mutant FbpAs retain significant iron-binding affinity rega...
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PMID: 20799927
PDF is available here.
Abstract
We followed two different approaches. In the first, we deleted the last eight amino acids of Hxk2 and replaced Ser³⁰⁴ with phenylalanine to generate Hxk2(wca). Analysis of this mutant demonstrated that these domains play an essential role in the catalytic activity of yeast Hxk2, but has no effe...
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PMID: 20815814
PDF is available here.
Abstract
We examined the interaction of kAE1 with the quality control system responsible for the folding of membrane glycoproteins and the retention and degradation of misfolded mutants. Using small molecule inhibitors to disrupt chaperone interactions, two functional, dominant kAE1 mutants (R589H and R901st...
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PMID: 20628050
PDF is available here.
Abstract
We report the first three-dimensional structure of the mammalian selenoprotein methionine sulfoxide reductase B1 (MsrB1), determined by high resolution NMR spectroscopy. Heteronuclear multidimensional spectra yielded NMR spectral assignments for the reduced form of MsrB1 in which catalytic selenocys...
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PMID: 20605785
PDF is available here.
Abstract
We have performed an in silico analysis of the conformational preference of this segment of caveolin-1 using PepLook. We find that there is one main group of stable conformations corresponding to a hydrophobic U bent model that would not traverse the membrane. Furthermore, the calculations predict t...
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PMID: 20729193
PDF is available here.
Abstract
We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfold...
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PMID: 20947758
PDF is available here.
Abstract
We report the solution NMR structure of the highly pathogenic, drug resistant mutant V27A. The structure reveals subtle structural differences from wildtype that maybe linked to drug resistance. The V27A mutation significantly decreases hydrophobic packing between the N-terminal ends of the transmem...
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PMID: 20833142
PDF is available here.
Abstract
We have developed a single 17-residue peptide immunogen that generates antibodies that target the receptor-binding domain of the type IV pilus of more than one strain of P. aeruginosa. Using the receptor-binding domain sequence, of native strain PAO as a template, we have systematically changed up...
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PMID: 20807222
PDF is available here.
Abstract
Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundam...
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PMID: 20960178
PDF is available here.
Abstract
Little is known about whether neuraminidase inhibitors are effective for children infected with oseltamivir-resistant influenza A(H1N1) viruses.
Children aged 15 years and younger having influenza-like illness and who visited outpatient clinics within 48 hours of fever onset were enrolled from 2006-...
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PMID: 20442686
PDF is available here.
Abstract
The Met-542 residue of β-galactosidase is important for the enzyme's activity because it acts as a guide for the movement of the benzyl side chain of Phe-601 between two stable positions. This movement occurs in concert with an important conformational change (open vs. closed) of an active site loo...
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PMID: 20921997
PDF is available here.
C Stephan,
B Dauer,
M Bickel,
A Haberl,
L Locher,
A Müller,
S Klauke,
A Berger,
H-W Doerr,
M Stürmer,
S Staszewski and
Frankfurt Cohort Study
Abstract
We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from pr...
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PMID: 20600301
PDF is available here.
Abstract
Our study reveals that interspecific gene flow affects the genome evolution in Arabidopsis.
© The Authors (2010). Journal compilation © New Phytologist Trust (2010)....
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PMID: 20673288
PDF is available here.
Abstract
We found that most pyrosequencing singletons were artifactual and contained a strongly elevated proportion of insertions compared with natural intra- and interspecific variation. The alternative primers, DNA extraction methods and PCR replicates strongly influenced the richness and community composi...
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PMID: 20636324
PDF is available here.
Abstract
We have employed a combination of cysteine mutagenesis and chemical crosslinking using a photoactivatable sulfhydryl reagent, benzophenone-4-maleimide, to obtain a covalent complex between human galectin-1 and a model glycoprotein ligand, asialofetuin. We previously obtained a crosslinked product wh...
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PMID: 20930491
PDF is available here.
Abstract
The Merlin gene of Drosophila is homologous to the human Neurofibromatosis 2 (NF2) gene an important regulator of proliferation and endocytosis of cell receptors. It was earlier shown that the Thr5 residue of the Drosophila Merlin protein was homologous to Ser518 of the human protein (which was alre...
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PMID: 21254560
PDF is available here.