The crystal structure of the enzyme 3-isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tu... more The crystal structure of the enzyme 3-isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tuberculosis (LeuB, Mtb-IPMDH, Rv2995c) without substrate or co-factor was determined at 1.65 Å resolution, which is the highest resolution reported for an IPMDH to date. The crystals contain two functional dimers in the asymmetric unit in an arrangement close to a tetramer of D 2 symmetry. Despite the absence of a substrate or inhibitor bound to the protein, the structure of the monomer resembles the previously observed closed form of the enzyme more closely than the open form. A comparison with the substrate complex of IPMDH from Thiobacillus ferrooxidans and the co-factor complex of the Thermus thermophilus enzyme revealed a close relationship of the active-site architecture between the various bacterial enzymes. The inhibitor O-isobutenyl oxalylhydroxamate was found to bind to the active site of IPMDH in a mode similar to the substrate isopropylmalate.
Mdm2 is a member of the RING finger family of ubiquitin ligases and is best known for its role in... more Mdm2 is a member of the RING finger family of ubiquitin ligases and is best known for its role in targeting the tumor suppressor p53 for ubiquitination and degradation. Mdm2 can bind to itself and to the structurally related protein MdmX, and these interactions involve the RING finger domain of Mdm2 and MdmX, respectively. In this study, we performed a mutational analysis of the RING finger domain of Mdm2, and we identified several amino acid residues that are important for Mdm2 to exert its ubiquitin ligase function. Mutation of some of these residues interfered with the Mdm2-Mdm2 interaction indicating that a homomeric complex represents the active form of Mdm2. Mutation of other residues did not detectably affect the ability of Mdm2 to interact with itself but reduced the ability of Mdm2 to interact with UbcH5. Remarkably, MdmX efficiently rescued the ubiquitin ligase activity of the latter Mdm2 mutants in vitro and within cells. Because the interaction of Mdm2 with MdmX is more stable than the Mdm2-Mdm2 interaction, this suggests that Mdm2-MdmX complexes play a prominent role in p53 ubiquitination in vivo. Furthermore, we show that, similar to Mdm2, the Mdm2-MdmX complex has Nedd8 ligase activity and that all mutations that affect the ubiquitin ligase activity of Mdm2 also affect its Nedd8 ligase activity. From a mechanistic perspective, this suggests that the actual function of Mdm2 and Mdm2-MdmX, respectively, in p53 ubiquitination and in p53 neddylation is similar for both processes.
Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killi... more Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
Alcohol dehydrogenases play an important role during fruit ripening and aroma production. Three f... more Alcohol dehydrogenases play an important role during fruit ripening and aroma production. Three fulllength cDNAs (MiAdh1, 2 and 3) encoding alcohol dehydrogenases were obtained from mango fruit pulp using RT-PCR approaches. All three members displayed strong homology in the coding region when compared at the protein and nucleotide levels, however showed variations in untranslated regions. Expression patterns of these ADHs were different during fruit development and ripening. MiADH1 and MiADH2 transcripts accumulated at the onset of ripening in mango fruit whereas MiADH3 accumulated during early development of fruit. Expression analysis also indicated that mango ADHs were responsive to ethylene but regulated differently by ABA. MiADH1 was induced by ABA treatment whereas MiADH2 transcript was negatively regulated by ABA. MiADH3 did not respond to ABA in ripening fruit. Differences in substrate specificity for NADH and NADPH were also observed between the three enzymes. Total ADH enzyme activity correlated positively with increased transcript levels at the initiation of ripening.
Journal of Biomolecular Structure & Dynamics, 2012
CC chemokine receptor type-2 (CCR2) is a member of G-protein coupled receptors superfamily, expre... more CC chemokine receptor type-2 (CCR2) is a member of G-protein coupled receptors superfamily, expressed on the cell surface of monocytes and macrophages. It binds to the monocyte chemoattractant protein-1, a CC chemokine, produced at the sites of inflammation and infection. A homology model of human CCR2 receptor based on the recently available C-X-C chemokine recepor-4 crystal structure has been reported. Ligand information was used as an essential element in the homology modeling process. Six known CCR2 antagonists were docked into the model using simple and induced fit docking procedure. Docked complexes were then subjected to visual inspection to check their suitability to explain the experimental data obtained from site directed mutagenesis and structure-activity relationship studies. The homology model was refined, validated, and assessed for its performance in docking-based virtual screening on a set of CCR2 antagonists and decoys. The docked complexes of CCR2 with the known antagonists, TAK779, a dual CCR2/CCR5 antagonist, and Teijin-comp1, a CCR2 specific antagonist were subjected to molecular dynamics (MD) simulations, which further validated the binding modes of these antagonists. B-factor analysis of 20 ns MD simulations demonstrated that Cys190 is helpful in providing structural rigidity to the extracellular loop (EL2). Residues important for CCR2 antagonism were recognized using free energy decomposition studies. The acidic residue Glu291 from TM7, a conserved residue in chemokine receptors, is favorable for the binding of Teijin-comp1 with CCR2 by ΔG of −11.4 kcal/mol. Its contribution arises more from the side chains than the backbone atoms. In addition, Tyr193 from EL2 contributes −0.9 kcal/mol towards the binding of the CCR2 specific antagonist with the receptor. Here, the homology modeling and subsequent molecular modeling studies proved successful in probing the structure of human CCR2 chemokine receptor for the structure-based virtual screening and predicting the binding modes of CCR2 antagonists.
Indian journal of clinical biochemistry : IJCB, 2013
Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukoc... more Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukocyte antigen class I allele HLA-B27. More than 90 % of patients with ankylosing spondylitis possess the HLA-B27 allele, but only 1 % of people with HLA-B27 develop the disease. Ankylosing spondylitis predominately affects young males. The present study was planned to find out the involvement of HLA-B27 specific allele in relation to age and sex in symptomatic suspected patients of ankylosing spondylitis using conventional PCR technology. Forty symptomatic patients of ankylosing spondylitis were included in the present study. SSP-PCR technique was used to detect the HLA-B27 specific allele. This study showed (out of 40 symptomatic suspected cases of ankylosing spondylitis only 12 patients were detected positive with HLA-B27 allele, while remaining 28 were negative) that the positivity rate for ankylosing spondylitis with HLA-B27 allele is low. Furthermore, it was observed that the males above 50 years are more prone to develop AS with HLA-B27 specific allele. It could be concluded that the conventional PCR technology is a rapid, sensitive, and confirmatory method for the diagnosis of ankylosing spondylitis.
Indian journal of clinical biochemistry : IJCB, 2013
Genitourinary tuberculosis is a disease of the genitourinary system which includes the entire uri... more Genitourinary tuberculosis is a disease of the genitourinary system which includes the entire urinary tract and reproductive system. Genital tuberculosis is an important cause of female infertility, especially in developing nations like India. In the present study, a total of 257 clinical specimens comprising of endometrial biopsy (109), endometrial curetting (42), menstrual blood (8), semen (17), placenta (11) and urine (70) were collected from patients and subjected for PCR, Culture and AFB detection. The endometrial biopsy, endometrial curetting, menstrual blood, semen, placenta, urine showed 30.2, 45.2,12.5, 5.8, 27.2, 31.4 %, positivity rate for tuberculosis by PCR, 7.3, 9.5, 25.0, 0, 9, 8.5 % by culture and 1.8, 2.3, 0, 0, 0, 2.8 % respectively by AFB smear. Being a novel, rapid technique, PCR is the method of choice for rapid diagnosis and management of genitourinary tuberculosis shared with the other concerned tests. This study reveals that genital tuberculosis can occur in any age group, however, the majority of patients were from reproductive age (nearly 75 % of them were from 20-45 years of age) group.
Angewandte Chemie (International ed. in English), Jan 10, 2014
Uncovering the mechanisms that allow conjugates of ubiquitin (Ub) and/or Ub-like (UBL) proteins s... more Uncovering the mechanisms that allow conjugates of ubiquitin (Ub) and/or Ub-like (UBL) proteins such as Rub1 to serve as distinct molecular signals requires the ability to make them with native connectivity and defined length and linkage composition. A novel, effective, and affordable strategy for controlled chemical assembly of fully natural UBL-Ub, Ub-UBL, and UBL-UBL conjugates from recombinant monomers is presented. Rubylation of Ub and Rub1 and ubiquitination of Rub1 was achieved without E2/E3 enzymes. New residue-specific information was obtained on the interdomain contacts in naturally-occurring K48-linked Rub1-Ub and Ub-Rub1, and K29-linked Rub1-Ub heterodimers, and their recognition by a K48-linkage-specific Ub receptor. The disassembly of these heterodimers by major deubiquitinating enzymes was examined and it was discovered that some deubiquitinases also possess derubylase activity. This unexpected result suggests possible crosstalk between Ub and Rub1/Nedd8 signaling pathways.
ABSTRACT In the present paper, we have studied the effect of soil textures, i.e., sand, silt and ... more ABSTRACT In the present paper, we have studied the effect of soil textures, i.e., sand, silt and clay on micro-wave scattering at X-band (10 GHz) at various incidence angles and like polarizations (i.e., Hori-zontal-Horizontal; HH-, Vertical-Vertical; VV-). We have proposed a retrieval technique based on Genetic Algorithm (GA) to retrieve soil texture. For this purpose, ten types of soil mixtures having different percentage of sand, silt and clay have been analyzed. The observations were carried out by ingeniously assembled X-band scatterometer. A good agreement has been noticed between es-timated and observed soil texture. Study infers that soil texture is quite sensitive to radar scatter-ing and it is possible to retrieve soil texture with radar/scatterometer data with good accuracy and this type of retrieved results can be helpful to predict soil strength as well as soil erosion of the particular area.
We report our investigations on Lanthanum Strontium Magnesium Gallate, LSGM, La 0.8 Sr 0.2 Ga 0.8... more We report our investigations on Lanthanum Strontium Magnesium Gallate, LSGM, La 0.8 Sr 0.2 Ga 0.8 Mg 0.2 O 3-į doped with Barium at Strontium site having composition La 0.8 (Sr 0.1 Ba 0.1 )Ga0 .8 Mg 0.2 O 3-į (LSBGM). The pure cubic phase along with some additional phase was confirmed by XRD pattern. Electrical properties of the Composition LSBGM [La 0.8 (Sr 0.1 Ba 0. 1)Ga0 .8 Mg 0.2 O 3-į ] prepared by solid state route, was studied employing impedance spectroscopy in the temperature range 573 K-993 K and frequency range 20 Hz-1MHz. The total ionic conductivity of the composition was found to be 0.072 S.cm -1 at 953 K and the activation energy from Arrhenius plot was found to be 1.16 eV in the measured temperature range. This confirms oxygen ion conductivity in the system. SEM micrograph shows the uniform densed particle morphology with gains of average size 200 nm.
2002 esterification, transesterification esterification, transesterification O 0315 29 -081 Lewis... more 2002 esterification, transesterification esterification, transesterification O 0315 29 -081 Lewis Acid Catalyzed Acylation Reactions: Scope and Limitations. -Copper(II) triflate is shown to be a versatile catalyst for the acylation of alcohols, phenols, thiols and carbohydrates. A wide range of different alcohols can be acylated, including sensitive alcohols like linalool (Xa). Additionally, the presented method is selective for primary hydroxy groups in the presence of secondary ones [cf. (XIV), (XVII)], and for secondary in the presence of tertiary hydroxy groups [cf. (XII)]. A probable catalytic cycle is presented and discussed. -(CHANDRA, KUSUM L.; SARAVANAN, P.; SINGH, RAJESH K.; SINGH, VINOD K.; Tetrahedron 58 (2002) 7, 1369-1374; Dep. Chem., Indian Inst. Technol., Kanpur 208 016, India; EN)
AbstractÐAcylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, an... more AbstractÐAcylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, and it was found that Cu-and Sn(OTf) 2 are very ef®cient in catalyzing the reaction under mild conditions. Among these two catalysts, Cu(OTf) 2 was preferred because of its lower cost and relatively higher yield of the acylated product. The reaction was studied in several solvents, but CH 2 Cl 2 was preferred. It was also observed that the present method is suitable for acylation of tertiary alcohols. Sugars were also acylated without any epimerization at the anomeric center. It is further shown here that this method is also suitable for selective acylation of primary or secondary alcohols over tertiary ones. q 2002 Elsevier Science Ltd. All rights reserved.
A new flavonol glycoside was isolated from roots of Pterocarpus marsupium. Its structure was dete... more A new flavonol glycoside was isolated from roots of Pterocarpus marsupium. Its structure was determined as 6-hydroxy-3,5,7,4'-tetramethoxyflavone 6-O-rhamnopyranoside by spectral data and chemical degradation.
Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show ... more Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show via NMR that structurally, Rub1 and ubiquitin are fundamentally similar as well. Despite these profound similarities, the prevalence of Rub1/Nedd8 and of ubiquitin as modifiers of the proteome is starkly different, and their attachments to specific substrates perform different functions. Recently, some proteins, including p53, p73, EGFR, caspase-7, and Parkin, have been shown to be modified by both Rub1/ Nedd8 and ubiquitin within cells. To understand whether and how it might be possible to distinguish among the same target protein modified by Rub1 or ubiquitin or both, we examined whether ubiquitin receptors can differentiate between Rub1 and ubiquitin. Surprisingly, Rub1 interacts with proteasome ubiquitin-shuttle proteins comparably to ubiquitin but binds more weakly to a proteasomal ubiquitin receptor Rpn10. We identified Rub1-ubiquitin heteromers in yeast and Nedd8-Ub heteromers in human cells. We validate that in human cells and in vitro, human Rub1 (Nedd8) forms chains with ubiquitin where it acts as a chain terminator. Interestingly, enzymatically assembled K48-linked Rub1-ubiquitin heterodimers are recognized by various proteasomal ubiquitin shuttles and receptors comparably to K48-linked ubiquitin homodimers. Furthermore, these heterologous chains are cleaved by COP9 signalosome or 26S proteasome. A derubylation function of the proteasome expands the repertoire of its enzymatic activities. In contrast, Rub1 conjugates may be somewhat resilient to the actions of other canonical deubiquitinating enzymes. Taken together, these findings suggest that once Rub1/Nedd8 is channeled into ubiquitin pathways, it is recognized essentially like
The crystal structure of the enzyme 3-isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tu... more The crystal structure of the enzyme 3-isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tuberculosis (LeuB, Mtb-IPMDH, Rv2995c) without substrate or co-factor was determined at 1.65 Å resolution, which is the highest resolution reported for an IPMDH to date. The crystals contain two functional dimers in the asymmetric unit in an arrangement close to a tetramer of D 2 symmetry. Despite the absence of a substrate or inhibitor bound to the protein, the structure of the monomer resembles the previously observed closed form of the enzyme more closely than the open form. A comparison with the substrate complex of IPMDH from Thiobacillus ferrooxidans and the co-factor complex of the Thermus thermophilus enzyme revealed a close relationship of the active-site architecture between the various bacterial enzymes. The inhibitor O-isobutenyl oxalylhydroxamate was found to bind to the active site of IPMDH in a mode similar to the substrate isopropylmalate.
Mdm2 is a member of the RING finger family of ubiquitin ligases and is best known for its role in... more Mdm2 is a member of the RING finger family of ubiquitin ligases and is best known for its role in targeting the tumor suppressor p53 for ubiquitination and degradation. Mdm2 can bind to itself and to the structurally related protein MdmX, and these interactions involve the RING finger domain of Mdm2 and MdmX, respectively. In this study, we performed a mutational analysis of the RING finger domain of Mdm2, and we identified several amino acid residues that are important for Mdm2 to exert its ubiquitin ligase function. Mutation of some of these residues interfered with the Mdm2-Mdm2 interaction indicating that a homomeric complex represents the active form of Mdm2. Mutation of other residues did not detectably affect the ability of Mdm2 to interact with itself but reduced the ability of Mdm2 to interact with UbcH5. Remarkably, MdmX efficiently rescued the ubiquitin ligase activity of the latter Mdm2 mutants in vitro and within cells. Because the interaction of Mdm2 with MdmX is more stable than the Mdm2-Mdm2 interaction, this suggests that Mdm2-MdmX complexes play a prominent role in p53 ubiquitination in vivo. Furthermore, we show that, similar to Mdm2, the Mdm2-MdmX complex has Nedd8 ligase activity and that all mutations that affect the ubiquitin ligase activity of Mdm2 also affect its Nedd8 ligase activity. From a mechanistic perspective, this suggests that the actual function of Mdm2 and Mdm2-MdmX, respectively, in p53 ubiquitination and in p53 neddylation is similar for both processes.
Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killi... more Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
Alcohol dehydrogenases play an important role during fruit ripening and aroma production. Three f... more Alcohol dehydrogenases play an important role during fruit ripening and aroma production. Three fulllength cDNAs (MiAdh1, 2 and 3) encoding alcohol dehydrogenases were obtained from mango fruit pulp using RT-PCR approaches. All three members displayed strong homology in the coding region when compared at the protein and nucleotide levels, however showed variations in untranslated regions. Expression patterns of these ADHs were different during fruit development and ripening. MiADH1 and MiADH2 transcripts accumulated at the onset of ripening in mango fruit whereas MiADH3 accumulated during early development of fruit. Expression analysis also indicated that mango ADHs were responsive to ethylene but regulated differently by ABA. MiADH1 was induced by ABA treatment whereas MiADH2 transcript was negatively regulated by ABA. MiADH3 did not respond to ABA in ripening fruit. Differences in substrate specificity for NADH and NADPH were also observed between the three enzymes. Total ADH enzyme activity correlated positively with increased transcript levels at the initiation of ripening.
Journal of Biomolecular Structure & Dynamics, 2012
CC chemokine receptor type-2 (CCR2) is a member of G-protein coupled receptors superfamily, expre... more CC chemokine receptor type-2 (CCR2) is a member of G-protein coupled receptors superfamily, expressed on the cell surface of monocytes and macrophages. It binds to the monocyte chemoattractant protein-1, a CC chemokine, produced at the sites of inflammation and infection. A homology model of human CCR2 receptor based on the recently available C-X-C chemokine recepor-4 crystal structure has been reported. Ligand information was used as an essential element in the homology modeling process. Six known CCR2 antagonists were docked into the model using simple and induced fit docking procedure. Docked complexes were then subjected to visual inspection to check their suitability to explain the experimental data obtained from site directed mutagenesis and structure-activity relationship studies. The homology model was refined, validated, and assessed for its performance in docking-based virtual screening on a set of CCR2 antagonists and decoys. The docked complexes of CCR2 with the known antagonists, TAK779, a dual CCR2/CCR5 antagonist, and Teijin-comp1, a CCR2 specific antagonist were subjected to molecular dynamics (MD) simulations, which further validated the binding modes of these antagonists. B-factor analysis of 20 ns MD simulations demonstrated that Cys190 is helpful in providing structural rigidity to the extracellular loop (EL2). Residues important for CCR2 antagonism were recognized using free energy decomposition studies. The acidic residue Glu291 from TM7, a conserved residue in chemokine receptors, is favorable for the binding of Teijin-comp1 with CCR2 by ΔG of −11.4 kcal/mol. Its contribution arises more from the side chains than the backbone atoms. In addition, Tyr193 from EL2 contributes −0.9 kcal/mol towards the binding of the CCR2 specific antagonist with the receptor. Here, the homology modeling and subsequent molecular modeling studies proved successful in probing the structure of human CCR2 chemokine receptor for the structure-based virtual screening and predicting the binding modes of CCR2 antagonists.
Indian journal of clinical biochemistry : IJCB, 2013
Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukoc... more Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukocyte antigen class I allele HLA-B27. More than 90 % of patients with ankylosing spondylitis possess the HLA-B27 allele, but only 1 % of people with HLA-B27 develop the disease. Ankylosing spondylitis predominately affects young males. The present study was planned to find out the involvement of HLA-B27 specific allele in relation to age and sex in symptomatic suspected patients of ankylosing spondylitis using conventional PCR technology. Forty symptomatic patients of ankylosing spondylitis were included in the present study. SSP-PCR technique was used to detect the HLA-B27 specific allele. This study showed (out of 40 symptomatic suspected cases of ankylosing spondylitis only 12 patients were detected positive with HLA-B27 allele, while remaining 28 were negative) that the positivity rate for ankylosing spondylitis with HLA-B27 allele is low. Furthermore, it was observed that the males above 50 years are more prone to develop AS with HLA-B27 specific allele. It could be concluded that the conventional PCR technology is a rapid, sensitive, and confirmatory method for the diagnosis of ankylosing spondylitis.
Indian journal of clinical biochemistry : IJCB, 2013
Genitourinary tuberculosis is a disease of the genitourinary system which includes the entire uri... more Genitourinary tuberculosis is a disease of the genitourinary system which includes the entire urinary tract and reproductive system. Genital tuberculosis is an important cause of female infertility, especially in developing nations like India. In the present study, a total of 257 clinical specimens comprising of endometrial biopsy (109), endometrial curetting (42), menstrual blood (8), semen (17), placenta (11) and urine (70) were collected from patients and subjected for PCR, Culture and AFB detection. The endometrial biopsy, endometrial curetting, menstrual blood, semen, placenta, urine showed 30.2, 45.2,12.5, 5.8, 27.2, 31.4 %, positivity rate for tuberculosis by PCR, 7.3, 9.5, 25.0, 0, 9, 8.5 % by culture and 1.8, 2.3, 0, 0, 0, 2.8 % respectively by AFB smear. Being a novel, rapid technique, PCR is the method of choice for rapid diagnosis and management of genitourinary tuberculosis shared with the other concerned tests. This study reveals that genital tuberculosis can occur in any age group, however, the majority of patients were from reproductive age (nearly 75 % of them were from 20-45 years of age) group.
Angewandte Chemie (International ed. in English), Jan 10, 2014
Uncovering the mechanisms that allow conjugates of ubiquitin (Ub) and/or Ub-like (UBL) proteins s... more Uncovering the mechanisms that allow conjugates of ubiquitin (Ub) and/or Ub-like (UBL) proteins such as Rub1 to serve as distinct molecular signals requires the ability to make them with native connectivity and defined length and linkage composition. A novel, effective, and affordable strategy for controlled chemical assembly of fully natural UBL-Ub, Ub-UBL, and UBL-UBL conjugates from recombinant monomers is presented. Rubylation of Ub and Rub1 and ubiquitination of Rub1 was achieved without E2/E3 enzymes. New residue-specific information was obtained on the interdomain contacts in naturally-occurring K48-linked Rub1-Ub and Ub-Rub1, and K29-linked Rub1-Ub heterodimers, and their recognition by a K48-linkage-specific Ub receptor. The disassembly of these heterodimers by major deubiquitinating enzymes was examined and it was discovered that some deubiquitinases also possess derubylase activity. This unexpected result suggests possible crosstalk between Ub and Rub1/Nedd8 signaling pathways.
ABSTRACT In the present paper, we have studied the effect of soil textures, i.e., sand, silt and ... more ABSTRACT In the present paper, we have studied the effect of soil textures, i.e., sand, silt and clay on micro-wave scattering at X-band (10 GHz) at various incidence angles and like polarizations (i.e., Hori-zontal-Horizontal; HH-, Vertical-Vertical; VV-). We have proposed a retrieval technique based on Genetic Algorithm (GA) to retrieve soil texture. For this purpose, ten types of soil mixtures having different percentage of sand, silt and clay have been analyzed. The observations were carried out by ingeniously assembled X-band scatterometer. A good agreement has been noticed between es-timated and observed soil texture. Study infers that soil texture is quite sensitive to radar scatter-ing and it is possible to retrieve soil texture with radar/scatterometer data with good accuracy and this type of retrieved results can be helpful to predict soil strength as well as soil erosion of the particular area.
We report our investigations on Lanthanum Strontium Magnesium Gallate, LSGM, La 0.8 Sr 0.2 Ga 0.8... more We report our investigations on Lanthanum Strontium Magnesium Gallate, LSGM, La 0.8 Sr 0.2 Ga 0.8 Mg 0.2 O 3-į doped with Barium at Strontium site having composition La 0.8 (Sr 0.1 Ba 0.1 )Ga0 .8 Mg 0.2 O 3-į (LSBGM). The pure cubic phase along with some additional phase was confirmed by XRD pattern. Electrical properties of the Composition LSBGM [La 0.8 (Sr 0.1 Ba 0. 1)Ga0 .8 Mg 0.2 O 3-į ] prepared by solid state route, was studied employing impedance spectroscopy in the temperature range 573 K-993 K and frequency range 20 Hz-1MHz. The total ionic conductivity of the composition was found to be 0.072 S.cm -1 at 953 K and the activation energy from Arrhenius plot was found to be 1.16 eV in the measured temperature range. This confirms oxygen ion conductivity in the system. SEM micrograph shows the uniform densed particle morphology with gains of average size 200 nm.
2002 esterification, transesterification esterification, transesterification O 0315 29 -081 Lewis... more 2002 esterification, transesterification esterification, transesterification O 0315 29 -081 Lewis Acid Catalyzed Acylation Reactions: Scope and Limitations. -Copper(II) triflate is shown to be a versatile catalyst for the acylation of alcohols, phenols, thiols and carbohydrates. A wide range of different alcohols can be acylated, including sensitive alcohols like linalool (Xa). Additionally, the presented method is selective for primary hydroxy groups in the presence of secondary ones [cf. (XIV), (XVII)], and for secondary in the presence of tertiary hydroxy groups [cf. (XII)]. A probable catalytic cycle is presented and discussed. -(CHANDRA, KUSUM L.; SARAVANAN, P.; SINGH, RAJESH K.; SINGH, VINOD K.; Tetrahedron 58 (2002) 7, 1369-1374; Dep. Chem., Indian Inst. Technol., Kanpur 208 016, India; EN)
AbstractÐAcylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, an... more AbstractÐAcylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, and it was found that Cu-and Sn(OTf) 2 are very ef®cient in catalyzing the reaction under mild conditions. Among these two catalysts, Cu(OTf) 2 was preferred because of its lower cost and relatively higher yield of the acylated product. The reaction was studied in several solvents, but CH 2 Cl 2 was preferred. It was also observed that the present method is suitable for acylation of tertiary alcohols. Sugars were also acylated without any epimerization at the anomeric center. It is further shown here that this method is also suitable for selective acylation of primary or secondary alcohols over tertiary ones. q 2002 Elsevier Science Ltd. All rights reserved.
A new flavonol glycoside was isolated from roots of Pterocarpus marsupium. Its structure was dete... more A new flavonol glycoside was isolated from roots of Pterocarpus marsupium. Its structure was determined as 6-hydroxy-3,5,7,4'-tetramethoxyflavone 6-O-rhamnopyranoside by spectral data and chemical degradation.
Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show ... more Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show via NMR that structurally, Rub1 and ubiquitin are fundamentally similar as well. Despite these profound similarities, the prevalence of Rub1/Nedd8 and of ubiquitin as modifiers of the proteome is starkly different, and their attachments to specific substrates perform different functions. Recently, some proteins, including p53, p73, EGFR, caspase-7, and Parkin, have been shown to be modified by both Rub1/ Nedd8 and ubiquitin within cells. To understand whether and how it might be possible to distinguish among the same target protein modified by Rub1 or ubiquitin or both, we examined whether ubiquitin receptors can differentiate between Rub1 and ubiquitin. Surprisingly, Rub1 interacts with proteasome ubiquitin-shuttle proteins comparably to ubiquitin but binds more weakly to a proteasomal ubiquitin receptor Rpn10. We identified Rub1-ubiquitin heteromers in yeast and Nedd8-Ub heteromers in human cells. We validate that in human cells and in vitro, human Rub1 (Nedd8) forms chains with ubiquitin where it acts as a chain terminator. Interestingly, enzymatically assembled K48-linked Rub1-ubiquitin heterodimers are recognized by various proteasomal ubiquitin shuttles and receptors comparably to K48-linked ubiquitin homodimers. Furthermore, these heterologous chains are cleaved by COP9 signalosome or 26S proteasome. A derubylation function of the proteasome expands the repertoire of its enzymatic activities. In contrast, Rub1 conjugates may be somewhat resilient to the actions of other canonical deubiquitinating enzymes. Taken together, these findings suggest that once Rub1/Nedd8 is channeled into ubiquitin pathways, it is recognized essentially like
Uploads
Papers by rajesh singh