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961.
The Sortase family of transpeptidase enzymes catalyzes sequence-specific ligation of proteins to the cell wall of Gram-positive bacteria. Here, we describe the application of recombinant Staphylococcus aureus Sortase A to attach a tagged model protein substrate (green fluorescent protein) to polystyrene beads chemically modified with either alkylamine or the in vivo Sortase A ligand, Gly-Gly-Gly, on their surfaces. Furthermore, we show that Sortase A can be used to sequence-specifically ligate eGFP to amino-terminated poly(ethylene glycol) and to generate protein oligomers and cyclized monomers using suitably tagged eGFP. We find that an alkylamine can substitute for the natural Gly3 substrate, which suggests the possibility of using the enzyme in materials applications. The highly specific and mild Sortase A-catalyzed reaction, based on small recognition tags unlikely to interfere with protein expression, thus represents a useful addition to the protein immobilization and modification tool kit. 相似文献
962.
An ERF transcription factor in Medicago truncatula that is essential for Nod factor signal transduction 总被引:1,自引:0,他引:1
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963.
Kolocouris N Zoidis G Foscolos GB Fytas G Prathalingham SR Kelly JM Naesens L De Clercq E 《Bioorganic & medicinal chemistry letters》2007,17(15):4358-4362
Spiro[aziridine-2,2'-adamantanes] 1 and 2, spiro[azetidine-2,2'-adamantanes] 3 and 5, spiro[azetidine-3,2'-adamantane] 13, spiro[piperidine-4,2'-adamantanes] 25 and 27, and spiro barbituric analog 18 were synthesized and tested for their anti-influenza A virus properties and for trypanocidal activity. The effect of ring size on potency was investigated. Piperidine 25 showed significant anti-influenza A virus activity, being 12-fold more active than amantadine, about 2-fold more active than rimantadine, and 54-fold more potent than ribavirin. It also proved to be the most active of the compounds tested against bloodstream forms of the African trypanosome, Trypanosoma brucei, being 1.5 times more potent than rimantadine and at least 25 times more active than amantadine. 相似文献
964.
Hu LY Du D Hoffman J Smith Y Fedij V Kostlan C Johnson TR Huang Y Kesten S Harter W Yue WS Li JJ Barvian N Mitchell L Lei HJ Lefker B Carroll M Dettling D Krieger-Burke T Samas B Yalamanchili R Lapham K Pocalyko D Sliskovic D Ciotti S Stoller B Hena MA Ding Q Maiti SN Stier M Welgus H 《Bioorganic & medicinal chemistry letters》2007,17(21):5983-5988
Synthesis, pharmacology, and pharmacokinetic profiles of (1R, 2S)-4-(2-cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile are reported. This compound demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model. 相似文献
965.
Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic hepatitis C 总被引:2,自引:0,他引:2
Subramanian GM Fiscella M Lamousé-Smith A Zeuzem S McHutchison JG 《Nature biotechnology》2007,25(12):1411-1419
Treatment regimens based on the use of interferon-alpha (IFN-alpha) remain the cornerstone of therapy for chronic hepatitis C virus infection, which affects nearly 170 million people worldwide. Treatment options include unmodified IFN-alpha given three times weekly or pegylated IFNs given once weekly. The albumin-fusion platform takes advantage of the long half-life of human albumin to provide a new treatment approach that allows the dosing frequency of IFN-alpha to be reduced in individuals with chronic hepatitis C. Albinterferon alpha-2b (alb-IFN), a recombinant polypeptide composed of IFN-alpha2b genetically fused to human albumin, has an extended half-life and early evidence indicates that it is efficacious and well tolerated. Pharmacodynamic modeling supports treatment with alb-IFN at 2- or 4-week intervals. Phase 3 registration trials are in progress. The albumin-fusion platform is currently being applied to other important bioactive peptides with short half-lives. These fusion proteins, which are at present in different phases of clinical development, might lead to improved therapies across a broad range of diseases. 相似文献
966.
Ashok Subramanian Hilary Birch Rita McAvinchey Adam Stacey-Clear 《International Seminars in Surgical Oncology : ISSO》2007,4(1):12
Background
Pagets disease of the nipple presents as an eczematous lesion, occurs in 1 – 4% of all female breast carcinoma cases and is invariably associated with underlying malignancy either overt or occult. The majority of these cases are invasive disease although 40–45% are associated with DCIS.Case presentation
A 39 year old lady presented to our unit with a palpable lump in the right breast. Radiological and histological investigation proved this to be an extensive area of Ductal Carcinoma in Situ (DCIS) for which she underwent a simple mastectomy and immediate latissimus dorsi flap reconstruction. Histology revealed high grade DCIS with 2 small foci of invasive carcinoma. At 1 year the patient represented with a nodule adjacent to the reconstruction scar which was proved on biopsy to be consistent with Paget's disease. This was proved on formal excision.Conclusion
In the absence of underlying breast or apocrine tissue this case details a case of Paget's disease of uncertain origin.967.
Subramanian M Chander R Krishna M Chattopadhyay S 《Biochimica et biophysica acta》2007,1770(1):143-149
In the presence of a nonlethal concentration of Cu(II), washed Escherichia coli ATCC8739 cells were killed by a novel tripyrrole 1, isolated as a red pigment from the Serratia sp. Cell killing was accompanied by a depletion in the potassium pools of the cells due to the damage to the cytoplasmic membrane, without any detectable DNA damage as revealed by the transformed plasmid DNA and phage induction assay. This revealed that the bactericidal activity of compound 1 in the presence of Cu(II) results from membrane damage. Induction of endogenous catalase in the E. coli cells increased their resistance against the combination of compound 1 and Cu(II). Although compound 1 alone generated large amount of reactive oxygen species (ROS), it did not show any cell killing against E. coli in the absence of Cu(II). The Cu(II)-dependent bactericidal activity of compound 1 was suppressed by ethylenediaminetetraacetate, bathocuproine, catalase and superoxide disumutase (SOD), but not by dimethyl sulfoxide. These findings suggest that recycling redox reactions between Cu(II) and Cu(I), involving compound 1 and hydrogen peroxide on the cell surface, must be important in the mechanism of the killing. Compound 1 alone showed selective bactericidal activity against the gram positive bacterium, Bacillus cereus ATCC 6630, possibly due to its differential cellular transport. 相似文献
968.
Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis 总被引:1,自引:0,他引:1
Crabtree B Thiyagarajan N Prior SH Wilson P Iyer S Ferns T Shapiro R Brew K Subramanian V Acharya KR 《Biochemistry》2007,46(42):11810-11818
Human angiogenin (ANG), the first member of the angiogenin family (from the pancreatic ribonuclease A superfamily) to be identified, is an angiogenic factor that induces neovascularization. It has received much attention due to its involvement in the growth of tumors and its elevated expression level in pancreatic and several other cancers. Recently the biological role of ANG has been shown to extend to the nervous system. Mutations in ANG have been linked with familial as well as sporadic forms of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder characterized by selective destruction of motor neurons. Furthermore, mouse angiogenin-1 has been shown to be expressed in the developing nervous system and during the neuronal differentiation of pluripotent stem cells. We have now characterized the seven variants of ANG reported in ALS patients with respect to the known biochemical properties of ANG and further studied the biological properties of three of these variants. Our results show that the ribonucleolytic activity of six of the seven ANG-ALS implicated variants is significantly reduced or lost and some variants also show altered thermal stability. We report a significant reduction in the cell proliferative and angiogenic activities of the three variants that we chose to investigate further. Our studies on the biochemical and structural features of these ANG variants now form the basis for further investigations to determine their role(s) in ALS. 相似文献
969.
Iso Y Spees JL Serrano C Bakondi B Pochampally R Song YH Sobel BE Delafontaine P Prockop DJ 《Biochemical and biophysical research communications》2007,355(3):700-706
Signaling via the type 1 insulin-like growth factor receptor (IGF1R) confers resistance to EGF receptor (EGFR) inhibitors. It is plausible that reciprocal EGFR compensation could mediate resistance to IGF1R inhibition, prompting us to investigate effects of IGF1R depletion on EGFR signaling in breast cancer cells expressing relatively high (MDA-MB-468) or low (MCF7) EGFR. Transient IGF1R knockdown induced enhanced phosphorylation of the EGFR and its effectors JNK, ERKs and STAT5, but this did not prevent apoptosis induction and inhibition of clonogenic survival following IGF1R knockdown. We used IGF1R shRNA to induce chronic IGF1R depletion, and achieved stable gene silencing in MCF-7 cells; here, EGFR overexpression led to EGFR hyperphosphorylation, again without abrogating survival inhibition after IGF1R knockdown. In both cell lines, dual receptor knockdown prevented EGFR hyperphosphorylation, but induced no greater inhibition of clonogenic survival than IGF1R knockdown alone. These results suggest that the EGFR cannot compensate for IGF1R depletion, and are encouraging for the strategy of IGF1R targeting. 相似文献
970.
Sarah G. Whaley Christopher D. Radka Chitra Subramanian Matthew W. Frank Charles O. Rock 《The Journal of biological chemistry》2021,297(6)
Bacterial fatty acid synthesis in Escherichia coli is initiated by the condensation of an acetyl-CoA with a malonyl-acyl carrier protein (ACP) by the β-ketoacyl-ACP synthase III enzyme, FabH. E. coli ΔfabH knockout strains are viable because of the yiiD gene that allows FabH-independent fatty acid synthesis initiation. However, the molecular function of the yiiD gene product is not known. Here, we show the yiiD gene product is a malonyl-ACP decarboxylase (MadA). MadA has two independently folded domains: an amino-terminal N-acetyl transferase (GNAT) domain (MadAN) and a carboxy-terminal hot dog dimerization domain (MadAC) that encodes the malonyl-ACP decarboxylase function. Members of the proteobacterial Mad protein family are either two domain MadA (GNAT-hot dog) or standalone MadB (hot dog) decarboxylases. Using structure-guided, site-directed mutagenesis of MadB from Shewanella oneidensis, we identified Asn45 on a conserved catalytic loop as critical for decarboxylase activity. We also found that MadA, MadAC, or MadB expression all restored normal cell size and growth rates to an E. coli ΔfabH strain, whereas the expression of MadAN did not. Finally, we verified that GlmU, a bifunctional glucosamine-1-phosphate N-acetyl transferase/N-acetyl-glucosamine-1-phosphate uridylyltransferase that synthesizes the key intermediate UDP-GlcNAc, is an ACP binding protein. Acetyl-ACP is the preferred glucosamine-1-phosphate N-acetyl transferase/N-acetyl-glucosamine-1-phosphate uridylyltransferase substrate, in addition to being the substrate for the elongation-condensing enzymes FabB and FabF. Thus, we conclude that the Mad family of malonyl-ACP decarboxylases supplies acetyl-ACP to support the initiation of fatty acid, lipopolysaccharide, peptidoglycan, and enterobacterial common antigen biosynthesis in Proteobacteria. 相似文献