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Shiv Nadar University

(SoNS) School of Natural Sciences

HisB, encoded by open reading frame Rv1601, possesses enzymatic activity as an imidazoleglycerol-phosphate dehydratase in the histidine-biosynthetic pathway of Mycobacterium tuberculosis. A recombinant form of HisB was crystallized in three crystal forms: crystals grown using 20% PEG 1500 as a precipitant belonged to either the cubic space group P432 or the tetragonal space group P4, while an orthorhombic crystal form belonging to space group P21212 was obtained using 15% PEG 5000 and 10 mM MnCl2 as precipitant. The structure of HisB in the orthorhombic crystal form was solved by the molecular-replacement method using the crystal structure of its Arabidopsis thaliana counterpart, which shares 47% sequence identity with Rv1601, as the search model. {\textcopyright} 2011 International Union of Crystallography. All rights reserved.

World University root node

Life Sciences

Fulltext

Acta Crystallographica Section F: Structural Biology and Crystallization Communications

HisB from Mycobacterium tuberculosis: Cloning, overexpression in Mycobacterium smegmatis, purification, crystallization and preliminary X-ray crystallographic analysis

Objectives: Stem cell factor receptor, c-kit, is considered to be the master signalling molecule of haematopoietic stem cells. It develops the orchestral pattern of haematopoietic cell lineages, seen by its varying degree of omnipresence in progenitors, lineage committed and mature cells. We have investigated the effect of over-expressing c-kit on early recovery of the haematopoietic compartment, in irradiated hosts.Materials and methods: Normal bone marrow cells (BMCs) were transfected with Kitwt (wild-type c-kit) or its variant Kitmu (asp814tyr) by electroporation. Lethally irradiated mice were transplanted with normal or transfected congeneic BMCs. The effect of ectopic expression of c-kit on haematopoietic cell recovery was determined by analysing donor-derived cells. Furthermore, effects of both types of c-kit over-expression on progenitor and lineage-committed cells were examined by flow cytometric analysis of Sca-1 and lineage-committed (Lin+) cells respectively.Results: Hyper-activating Kitmu significantly improved recovery of the haematopoietic system in irradiated hosts. In vivo results showed that the donor-derived c-kit+ cell population was increased to more than 3-fold in the case of Kitmu-transfected cells compared to normal and Kitwt over-expressing BMCs. In general, survival of progenitor and committed cell was improved in the Kitmu over-expressing system compared to the other two cohorts.Conclusion: These results suggest that recruitment of the hyper-activating variant of c-kit (Kitmu) lead to early recovery of the bone marrow of lethally irradiated mice. © 2010 Blackwell Publishing Ltd.

Cell Proliferation

Foe turned friend: Multiple functional roles attributable to hyper-activating stem cell factor receptor mutant in regeneration of the haematopoietic cell compartment

The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion. © 2011 European Molecular Biology Organization.

EMBO Reports

Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex

Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT m = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a K a = 16.2±0.6×10 7 M -1 where enthalpic change ΔH = -13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = -2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (K a = 3.1±0.4×10 7 M -1) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding. © 2011 Kumar et al.

PLoS ONE

Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over rev peptide is mainly enthalpic in origin

Photostability is one of the key issues in NIR dyes and we have previously reported a photostable CyNA library. Herein we report an ultra-photostable cyanine-based NIR fluorescence library, CyR, utilizing the stability component of CyNA. Efficient solid phase chemistry was also devised to provide a robust synthetic route to the new library. © The Royal Society of Chemistry 2011.

Chemistry

RSC Advances

Solid phase synthesis of ultra-photostable cyanine NIR dye library

A NIR death experience: A highly photostable NIR protein-labeling dye (CyNE790) that maintained excellent fluorescent properties after protein conjugation has been synthesized. Furthermore, the adequacy of the dye for NIR imaging was confirmed by showing that the recognition properties of a labeled anti-EGFR antibody remained unaffected. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemistry - An Asian Journal

A photostable near-infrared protein labeling dye for in vivo imaging

A highly efficient enantioselective SNAr reaction of chiral acyl bicyclic lactam with substituted-2,4-dinitrobenzenes was developed, affording products containing quarternary stereogenic centers. They are further utilized towards an enantioselective synthesis of spirooxoindoles. © 2011 The Royal Society of Chemistry.

Organic and Biomolecular Chemistry

Enantioselective synthesis of spirooxoindoles via chiral auxiliary (bicyclic lactam) controlled SNAr reactions

Structural biology of kinase and in particular of tyrosine kinase has given detailed insights into the intrinsic flexibility of the catalytic domain and has provided a rational basis for obtaining selective inhibitors. In this paper, we have studied the conformational flexibility of c-Abl tyrosine kinase complexed with Imatinib (STI), in the presence of TIP3P water in physiological conditions at neutral pH. The conformational studies suggest that the flexibility of activation loop is responsible to facilitate the nucleotide binding and release. Owing to the conformational adaptability, adenosine triphosphate (ATP) binds at a particular site in the loop region of the tyrosine kinase. The molecular mechanics Poisson- Boltzmann surface area methods are analysed, as is a free-energy pathways method, which shows the stable binding with free energy 26.04 kcal/mol for STI. The binding energy calculated by the Sietraj method is approximately the same as the experimental binding energy of STI with c-Abl kinase. It is suggested that the conserved glutamic acid and lysine residues are necessary for the stability and optimum activity of inhibitor. This study may be helpful in rational drug designing of new kinase inhibitors. © 2011 Taylor & Francis.

Molecular Simulation

Conformational flexibility and binding energy profile of c-Abl tyrosine kinase complexed with Imatinib: An insight from MD study

Graphene samples with 1, 2, and 4 layers and 1 + 1 folded bi-layers and graphite have been irradiated with 2 MeV protons at fluences ranging from 1 × 1015 to 6 × 1018 ions/cm2. The samples were characterized using visible and UV Raman spectroscopy and Raman microscopy. The ion-induced defects were found to decrease with increasing number of layers. Graphene samples suspended over etched holes in SiO 2 have been fabricated and used to investigate the influence of the substrate SiO2 for defect creation in graphene. While Raman vibrational modes at 1460 cm-1 and 1555 cm-1 have been observed in the visible Raman spectra of substantially damaged graphene samples, these modes were absent in the irradiated-suspended monolayer graphene. © 2011 American Institute of Physics.

Physics

Journal of Applied Physics

Mega-electron-volt proton irradiation on supported and suspended graphene: A Raman spectroscopic layer dependent study

New push-pull copolymers based on thiophene (donor) and benzothiadiazole (acceptor) units, poly[4,7-bis(3-dodecylthiophene-2-yl) benzothiadiazole-co- thiophene] (PT3B1) and poly[4,7-bis(3-dodecylthiophene-2-yl) benzothiadiazole-co-benzothiadiazole] (PT2B2), are designed and synthesized via Stille and Suzuki coupling routes respectively. Gel permeation chromatography shows the number average molecular weights are 31100 and 8400 g mol-1 for the two polymers, respectively. Both polymers have shown absorption throughout a wide range of the UV-vis region, from 300 to 650 nm. A significant red shift of the absorption edge is observed in thin films compared to solution of the copolymers; the optical band gap is in the range of 1.7 to 1.8 eV. Cyclic voltammetry indicates reversible oxidation and reduction processes with HOMO energy levels calculated to be in the range of 5.2 to 5.4 eV. Upon testing both materials for organic field-effect transistors (OFETs), PT3B1 showed a hole mobility of 6.1 × 10-4 cm2 V-1 s -1, while PT2B2 did not show any field effect transport. Both copolymers displayed a photovoltaic response when combined with a methanofullerene as an electron acceptor. The best performance was achieved when the copolymer PT3B1 was blended with [70]PCBM in a 1:4 ratio, exhibiting a short-circuit current of 7.27 mA cm-2, an open circuit voltage of 0.85 V, and a fill factor of 41% yielding a power conversion efficiency of 2.54% under simulated air mass (AM) 1.5 global (1.5 G) illumination conditions (100 mW cm-2). Similar devices utilizing PT2B2 in place of PT3B1 demonstrated reduced performance with a short-circuit current of 4.8 mA cm -2, an open circuit voltage of 0.73 V, and a fill factor of 30% resulting in a power conversion efficiency of roughly 1.06%. © 2011 The Royal Society of Chemistry.

Journal of Materials Chemistry

Thiophene-benzothiadiazole-thiophene (D-A-D) based polymers: Effect of donor/acceptor moieties adjacent to D-A-D segment on photophysical and photovoltaic properties