Abstract
We show that Rrn7, a subunit of the yeast Pol I core factor, and its human ortholog TAF1B are TFIIB-like factors. Although distantly related, Rrn7 shares many activities associated with TFIIB-like factors. Domain swaps between TFIIB-related factors show that Rrn7 is most closely related to the Pol I...
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PMID: 21921198
PDF is available here.
Abstract
We have shown previously that deficiency of another peptidyl prolyl isomerase, FK506 binding protein 12/12.6, alters endothelial NO synthase phosphorylation and causes endothelial dysfunction and hypertension. Endothelial NO synthase contains the Pin1 binding sequence at (p)serine 116-proline 117 an...
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PMID: 21810655
PDF is available here.
Abstract
The V600E mutation in the BRAF oncogene is associated with colorectal carcinomas, with mismatch-repair deficiency and, recently, with nonresponse to epidermal growth factor receptor inhibitor therapy. The use of reliable techniques for its detection is important. The aim of our study...
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PMID: 21708284
PDF is available here.
Abstract
We determined the crystal structures of reovirus attachment protein σ1 in complex with α-2,3-sialyllactose, α-2,6-sialyllactose, and α-2,8-di-siallylactose. All three oligosaccharides terminate in sialic acid, which serves as a receptor for the reovirus serotype studied here. The overall structu...
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PMID: 21829363
PDF is available here.
Abstract
We previously reported on two Arabidopsis mutants, rus1 and rus2, that are hypersensitive to trace amounts of UV-B light. We performed mutagenesis screens for second-site suppressors of the rus mutant phenotype and identified mutations in the ASPARTATE AMINOTRANSFERASE2 (ASP2) gene. ASP2 encodes for...
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PMID: 21511809
PDF is available here.
Abstract
We present the crystal structures of the SECRET domain of vTNFR CrmD encoded by ectromelia virus and its complex with chemokine CX3CL1. The SECRET domain adopts a β-sandwich fold and utilizes its β-sheet I surface to interact with CX3CL1, representing a new chemokine-binding manner of viral CKBPs....
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PMID: 21829356
PDF is available here.
Abstract
We studied a middle-aged/elderly sample of 4,193 nondiabetic Japanese subjects stratified according gender (1,911 women and 2,282 men). The LEPR Gln223Arg (rs1137101) variant as well as both ADRB2 Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms were analyzed. The primary outcome was the...
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PMID: 21233812
PDF is available here.
Abstract
We assess the impact of the F610A mutation on the functionality of AcrB by means of computational techniques, using doxorubicin as substrate. We found that the compound slides deeply inside the binding pocket after mutation, increasing the strength of the interaction. During subsequent conformationa...
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PMID: 21707050
PDF is available here.
Wen-Ya WY Ko,
Kristin A KA Kaercher,
Emanuela E Giombini,
Paolo P Marcatili,
Alain A Froment,
Muntaser M Ibrahim,
Godfrey G Lema,
Thomas B TB Nyambo,
Sabah A SA Omar,
Charles C Wambebe,
Alessia A Ranciaro,
Jibril B JB Hirbo and
Sarah A SA Tishkoff
Abstract
We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes a...
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PMID: 21664997
PDF is available here.
Abstract
We compare the functional immunologic consequences of "conventional" complement deficiencies with these newly described developmental roles....
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PMID: 21664996
PDF is available here.
Abstract
A homology model for pig liver esterase was generated on the basis of human carboxyl esterase (hCE) and subjected to extensive molecular dynamics simulations. By virtual mutations the isoenzymes PLE1-6 and APLE were obtained, and the PLE1 trimer was built from the respective model of...
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PMID: 20862595
PDF is available here.
Abstract
We investigated whether variants in major candidate genes for food intake and body weight regulation contribute to obesity-related traits under a multilocus perspective. We studied 375 Brazilian subjects from partially isolated African-derived populations (quilombos). Seven variants displaying confl...
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PMID: 21233811
PDF is available here.
Abstract
We show that mutations at nine contact residues reduce the ability of the LDLR to support lipoprotein uptake. Unexpectedly, only four of the mutations (W515A, W541A, H562Y and H586Y) impaired acid-dependent lipoprotein release. The remaining mutations decreased the lipoprotein-binding capacity of th...
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PMID: 21511053
PDF is available here.
Abstract
We provide evidence that the oxidation state of the disulfide bond within a loop domain peptide determines its activity. The oxidized (closed) form inhibits fusion, while the reduced (opened) form enhances hemifusion. These opposite activities reach 60% difference in viral fusion. Both forms of the...
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PMID: 21429941
PDF is available here.
Abstract
We replaced conserved residues at the dimer interface to design a heterodimer with increased stability. One E2R mutant in which histidine was replaced by a glutamate residue showed preferential heterodimer formation in vitro, as well as an increase in plasticity at the interface, as a result of hist...
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PMID: 21482558
PDF is available here.
Abstract
We would like to evaluate whether overexpression of wild-type or mutant α-SYN might affect cAMP/PKA-dependent TH activation in DA-producing SK-N-BE(2)C cells. Here we show that wild-type and mutant A30P and A53T α-SYN attenuate forskolin-induced TH up-regulation, but do not suppress TH basal expre...
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PMID: 21656370
PDF is available here.
Abstract
The plasma phospholipid transfer protein (PLTP) plays a key role in lipid and lipoprotein metabolism. It has six potential N-glycosylation sites. To study the impact of these sites on PLTP secretion and activity, six variants containing serine to alanine point mutations were prepared by site-directed...
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PMID: 21515415
PDF is available here.
Danai D Bem,
Shin-Ichiro S Yoshimura,
Ricardo R Nunes-Bastos,
Frances F FF Bond,
Manju A MA Kurian,
Fatima F Rahman,
Mark T W MT Handley,
Yavor Y Hadzhiev,
Imran I Masood,
Ania A AA Straatman-Iwanowska,
Andrew R AR Cullinane,
Alisdair A McNeill,
Shanaz S SS Pasha,
Gail A GA Kirby,
Katharine K Foster,
Zubair Z Ahmed,
Jenny E JE Morton,
Denise D Williams,
John M JM Graham,
William B WB Dobyns,
Lydie L Burglen,
John R JR Ainsworth,
Paul P Gissen,
Ferenc F Müller,
Eamonn R ER Maher,
Francis A FA Barr and
Irene A IA Aligianis
Abstract
We performed autozygosity mapping in five consanguineous families without RAB3GAP1/2 mutations and identified loss-of-function mutations in RAB18. A c.71T > A (p.Leu24Gln) founder mutation was identified in four Pakistani families, and a homozygous exon 2 deletion (predicted to result in a frameshif...
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PMID: 21473985
PDF is available here.
Abstract
The BRAF(T1799A) mutation is reported to be associated to aggressive, persistent, and recurrent tumor in papillary thyroid carcinoma (PTC) patients. Association of the BRAF(T1799A) mutation in the primary tumor with the clinicopathological characteristics of PTC patients was analyzed...
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PMID: 21441079
PDF is available here.
Abstract
We compared the distribution of pathogenicity scores observed on the human phylogenetic tree to the distribution of all possible protein variations to define a measure of the effect of selection on these protein variations. The measured effect of selection increased exponentially with increasing pat...
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PMID: 21457906
PDF is available here.
Abstract
The assembly of mitochondrial respiratory chain complex IV (cytochrome c oxidase) involves the coordinated action of several assembly chaperones. In Saccharomyces cerevisiae, at least 30 different assembly chaperones have been identified. To date, pathogenic mutations leading to a mitochondrial disor...
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PMID: 21457908
PDF is available here.
Abstract
As a serine/threonine protein kinase, glycogen synthase kinase 3β (GSK3β) is an essential component of several cellular processes, including insulin, growth factor, and Wnt signaling. The conserved K85 is important to GSK3β activity and FRATide binding. To elucidate the mechanisms concerning kinas...
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PMID: 21442609
PDF is available here.
Abstract
We have developed a system for orthogonal control of the expression of mcjA and mcjD, thus permitting independent control of MccJ25 production and export/immunity in E. coli. We used this system to screen saturation mutagenesis libraries targeted to either the ring or tail portions of MccJ25 and dis...
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PMID: 21391585
PDF is available here.
Abstract
These results suggest that the rotavirus VP6, NSP1 and NSP5 genes of Wa-like rotaviruses are more prone to temporal mutations. Both structural and nonstructural genes of the Western Indian rotavirus strains shared nucleotide and amino acid substitutions with the Bangladeshi strain, Dhaka16-03 (G1P[8...
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PMID: 21256248
PDF is available here.
Abstract
We hypothesized that altered expression or function of MAVS, a key molecule downstream of the viral sensors RIG-I and MDA-5, may impair antiviral cell signalling and thereby influence the risk for systemic lupus erythematosus (SLE), the prototype autoimmune disease. We used molecular techniques to s...
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PMID: 21268286
PDF is available here.
Abstract
We examined the molecular basis of iron overload in a family of Vietnamese origin, characterized the molecular and cellular defect, and correlated it with the clinical and pathological phenotype.
We analyzed the ferroportin gene by DNA sequencing. The molecular characterization was p...
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PMID: 21094556
PDF is available here.
Abstract
We characterized an active site variant (Glu473Gln) in which partitioning between aldehyde release versus carboligation is inverted with an up to 100-fold preference for the latter pathway. Due to a defective protonation of the central carbanion/enamine intermediate, substrate turnover stalls at thi...
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PMID: 21341803
PDF is available here.
Abstract
The insect sodium channel is of particular interest for evaluating resistance to pyrethroids because it is the target molecule for this major class of neurotoxic insecticides. The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), sodium channel coding sequence representing domains IS6 through...
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PMID: 21404865
PDF is available here.
Abstract
We have previously shown that mutation of group-conserved residues present on transmembrane helices H2-H4 in the β(2)-adrenergic receptor (β(2)-AR) can influence both receptor expression and function. We now target the group-conserved sites, Gly315(7.42) and Ser319(7.46), on H7 for structure-funct...
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PMID: 21262196
PDF is available here.
Abstract
We have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1.
Pharmacological inhibition of JAK2/STAT5 signaling in JAK2V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell prolifer...
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PMID: 21247487
PDF is available here.
Abstract
We studied the reactions of wild type (WT) methMb and its alanine mutant at Cys110 (C110A) with H(2)O(2), particularly in the presence of reduced glutathione (GSH) which is well known as a reducing agent. The formation rates of the ferryloxo (Fe(IV)=O) species by H(2)O(2) under air were about the sa...
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PMID: 21256983
PDF is available here.
Abstract
The proton-coupled transporter (PCFT) mediates intestinal folate absorption and folate transport from blood across the choroid plexus. The membrane topology of PCFT has been defined using the substituted cysteine accessibility method; an intramolecular disulfide bond between the Cys 66 and 298 residu...
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PMID: 21256110
PDF is available here.
Abstract
To study association of gene TP53 polymorphic marker Pro72Arg coding synthesis of p53 protein with onset, course and progress of chronic glomerulonephritis (CGN).
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PMID: 21786572
PDF is available here.
Abstract
We generated mutant HIV-2 viruses, each carrying one of the remaining 17 possible amino acid residues, and examined their sensitivity to CM TRIM5α-mediated restriction. Results showed that hydrophobic residues or those with ring structures were associated with sensitivity, while those with small si...
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PMID: 21829511
PDF is available here.
Abstract
We report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, whi...
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PMID: 21674060
PDF is available here.
Abstract
We now have a tremendous opportunity to better understand which genes are the most variable or conserved, and what their particular functions and evolutionary dynamics are, through comparative genomics.
We chose human and eleven other high-coverage mammalian genome data-as well as an...
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PMID: 21342519
PDF is available here.
Author(s) unavailable
Abstract
Product of polymerase chain reaction designated as PKPIJ-B was isolated after amplification from genomic DNA of potato (Solarium tuberosum L., Zhukov Jubilee cultivar) using the designed primers. Nucleotide sequence of PKPIJ-B was determined and amino acid sequence of protein was restored. Analysis o...
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PMID: 21950113
PDF is available here.
Abstract
Apical membrane antigen 1 (AMA1) is essential for malaria parasite invasion of erythrocytes and is therefore an attractive target for drug development. Peptides that bind AMA1 have been identified from random peptide libraries expressed on the surface of phage. Of these, R1, which binds to a hydropho...
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PMID: 21213258
PDF is available here.
Abstract
We demonstrated that the stability of the N-terminal helix bundle structure is modulated by proline substitution at the most hydrophobic region (residues around Y18) in the N-terminal domain. Here we examine the effect of proline substitution at S55 located in another relatively hydrophobic region c...
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PMID: 21040803
PDF is available here.
Abstract
We demonstrate a physical association of RTE1 and ETR1 using in vivo and in vitro methods. Interaction of RTE1 and ETR1 was revealed in vivo by bimolecular fluorescence complementation (BiFC) in a tobacco cell transient assay and in stably transformed Arabidopsis. The association was also observed u...
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PMID: 20952388
PDF is available here.
Abstract
We used site-directed mutagenesis, UV spectroscopy, and x-ray crystallography to examine the catalytic role of Arg-104 and Arg-31. Exchange of Arg-104 with Ala, Ser, Thr, or Lys abolished 94.3-99.9% of the specific activity against LTA(4). Steady-state kinetics of R104A and R104S revealed that the K...
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PMID: 20980252
PDF is available here.
Abstract
We have determined the human male specific lethal 3 (hMSL3) chromo-barrel domain structure by x-ray crystallography to a resolution of 2.5 Å (r = 0.226, R(free) = 0.270). hMSL3 contains a canonical methyllysine binding pocket made up of residues Tyr-31, Phe-56, Trp-59, and Trp-63. A six-residue in...
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PMID: 20943666
PDF is available here.
Abstract
We present a spatial structure of a complex of the Ca(2+)-regulated photoprotein clytin with its green-fluorescent protein (cgGFP) from the jellyfish Clytia gregaria, and show that it accounts for the bioluminescence properties of this system in vitro. We adopted an indirect approach of combining x-...
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PMID: 20926380
PDF is available here.
Abstract
We showed that both isoforms of GSK-3 are important for mediating neuronal apoptosis. Nonphosphorylatable GSK-3α/β mutants (S21A/S9A) promoted apoptosis, whereas a peptide encompassing Ser-9 of GSK-3β protected neurons in a phosphorylation-dependent manner; these results indicate a critical role...
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PMID: 20841359
PDF is available here.
Abstract
We asked whether Nef variants selected under CTL-mediated selective pressure in vivo may constrain these important Nef activities. The analysis of autologous nef sequences isolated from a cohort of total 235 subjects in Japan revealed that the subjects showing amino acid variations, such as Arg75Thr...
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PMID: 21093412
PDF is available here.
Abstract
We used limited proteolysis to identify an exposed and flexible region in IAPP monomer. This region includes position 20 where a serine-to-glycine substitution (S20G) is associated with enhanced formation of amyloid fibrils and early onset type 2 diabetes. To perform detailed biophysical studies of...
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PMID: 21138275
PDF is available here.
Abstract
Influenza surveillance was implemented in Kolkata, eastern India in 2005 to identify the circulating subtypes and characterize their genetic diversity. Throat and nasal swabs were collected from outpatients with influenza-like illness (ILI). Of 2844 ILI cases identified at two referr...
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PMID: 20678590
PDF is available here.
Abstract
To facilitate mutagenesis study, it is necessary to be able to derive mutation targets and associated substitution rates in the sequence of interest regardless of the availability of corresponding structure. It is also important to obtain these data depending on the specific aims of the mutation pro...
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PMID: 20919756
PDF is available here.
Abstract
We analyze the function of two substitutions in mitochondrial targeting sequences that occurred and rose to high frequency recently during recent human evolution. The ancestral and modern versions of the two targeting sequences do not differ in the efficiency with which they direct a protein to the...
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PMID: 20977882
PDF is available here.
Abstract
Tumor protein D52 is expressed at high levels in exocrine cells containing large secretory granules where it regulates Ca(2+)-dependent protein secretion; however, D52 expression is also highly induced in multiple cancers. The present study investigated a role for the Ca(2+)-dependent phosphorylatio...
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PMID: 20946871
PDF is available here.
Abstract
The present study demonstrates that population-dependent differences in allele frequencies associated with health disparities provide a valuable framework for the interrogation of complex diseases in all populations.
© 2010 Wiley-Liss, Inc....
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PMID: 20593380
PDF is available here.
Abstract
We observed that mutation of the V225 position, apart from the processing sites, conferred an unusual property on PcyA; V225D mutant protein could bind BV and its analog BV13, but these complexes showed a distinct UV-vis absorption spectrum from that of the wild-type PcyA-BV complex. The crystal str...
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PMID: 20946883
PDF is available here.
Abstract
We employed Cys-scanning analysis of the xanthine-specific homolog YgfO from Escherichia coli. Using a functional mutant devoid of Cys residues (C-less), each amino acid residue in sequences (259)FLVVGTIYLLSVLEAVGDITATAMVSRRPIQGEEYQSRLKGGVLADGLVSVIASAV(314) and (342)TIAVMLVILGLFP(354) including thes...
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PMID: 20802252
PDF is available here.
Abstract
We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agoni...
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PMID: 20826780
PDF is available here.
Abstract
We identified the serine residue regulating SHIP1 activity. After mass spectrometric identification of 17 serine and threonine residues on SHIP1 as being phosphorylated by PKA in vitro, studies with truncation mutants of SHIP1 narrowed the phosphorylation site to the catalytic region between residue...
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PMID: 20810657
PDF is available here.
Emma Salomonsson,
Michael C Carlsson,
Veronica Osla,
Ruth Hendus-Altenburger,
Barbro Kahl-Knutson,
Christopher T Oberg,
Anders Sundin,
Rickard Nilsson,
Eva Nordberg-Karlsson,
Ulf J Nilsson,
Anna Karlsson,
James M Rini and
Hakon Leffler
Abstract
We have now produced 10 mutants of human galectin-3, with changes in these adjacent sites that have altered carbohydrate-binding fine specificity but that retain the basic β-galactoside binding activity as shown by glycan-array binding and a solution-based fluorescence anisotropy assay. Each mutant...
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PMID: 20807768
PDF is available here.