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排序方式: 共有776条查询结果,搜索用时 15 毫秒
691.
Jaroszewski L Schwarzenbacher R McMullan D Abdubek P Agarwalla S Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Deacon AM DiDonato M Elsliger MA Godzik A Grittini C Grzechnik SK Hale J Hampton E Han GW Haugen J Hornsby M Klock HE Koesema E Kreusch A Kuhn P Lesley SA Miller MD Moy K Nigoghossian E Paulsen J Quijano K Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2005,61(3):669-673
692.
Han GW Schwarzenbacher R McMullan D Abdubek P Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Dai X Deacon AM DiDonato M Elsliger MA Godzik A Grittini C Grzechnik SK Hale J Hampton E Haugen J Hornsby M Jaroszewski L Klock HE Koesema E Kreusch A Kuhn P Lesley SA McPhillips TM Miller MD Moy K Nigoghossian E Paulsen J Quijano K Reyes R Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2005,60(4):797-802
693.
Tałalaj M Kapitan-Malinowska B Debski K Nowakowski R Marcinowska-Suchowierska E Witeska A 《Endokrynologia Polska》2005,56(3):225-232
Complete androgenic blockade used in the treatment of advanced prostatic carcinoma can be attained by administration of antiandrogens in orchidectomized patients or by combined therapy with LH-RH analogs and antiandrogens. The treatment, however, decreases the influence of both androgens end estrogens on bone tissue and may result in bone mass loss and increased propensity to fractures. The purpose of the study was to determine the influence of complete androgenic blockade on bone mass and skeletal metabolism in men with advanced prostatic carcinoma and to assess whether 1alpha-OH vitamin D3 (1alpha-OHD3) together with calcium supplementation is able to prevent bone mass loss in men treated with complete androgenic blockade. 51 patients with advanced prostatic carcinoma, with skeletal metastases, aged 44 - 86, mean 68 ys were included into a 12-month prospective study. All patients were treated with orchidectomy followed by therapy with flutamide in a dose of 750 mg daily. 26 patients were additionally given 1alpha-OHD3 in a dose of 0.5 microg/d and calcium carbonate in an initial dose of 1 g daily. It was found that the 12-month treatment with complete androgenic blockade resulted in a decrease in bone mineral density (BMD) by 8.1% in the lumbar spine, by 6.3% in the femoral neck and by 3.5% in the total skeleton. Therapy with 1alpha-OHD3 and CaCO3 caused complete inhibition of bone tissue loss in the lumbar spine and resulted in an increase in BMD by 2.2% in femoral neck and by 1.9% in the total skeleton. None of the examined patients experienced any skeletal fractures. In both groups of patients a prompt decrease in serum alkaline phosphatase activity - a marker of osteoblast activity and an increase in fasting urine calcium creatinine ratio indicating acceleration of bone resorption were found. Conclusions: in patients with advanced prostatic carcinoma treated with complete androgenic blockade acceleration of bone mass loss is observed; treatment with 1alpha-OHD3 and CaCO3 is able to prevent both trabecular and compact bone loss. 相似文献
694.
695.
The X-ray crystal structure of human prostatic acid phosphatase (PAP) in complex with a phosphate ion has been determined at 2.4 A resolution. This structure offers a snapshot of the final intermediate in the catalytic mechanism and does not support the role of Asp 258 as a proton donor in catalysis. A total of eight hydrogen bonds serve to strongly bind the phosphate ion within the active site. Bound PEG molecules from the crystallization matrix have allowed the identification of a channel within the molecule that likely plays a role in molecular recognition and in macromolecular substrate selectivity. Additionally, the structure of PAP in complex with a phosphate derivative, alpha-benzylaminobenzylphosphonic acid, a potent inhibitor (IC(50) = 4 nM), has been determined to 2.9 A resolution. This structure gives new insight into the determinants of binding hydrophobic ligands within the active site and allows us to explain PAP's preference for aromatic substrates. 相似文献
696.
Structure of small protein B: the protein component of the tmRNA-SmpB system for ribosome rescue 总被引:4,自引:0,他引:4
Small protein B (SmpB) is an essential component of the highly conserved tmRNA-SmpB system that has the dual function of releasing stalled ribosomes from damaged messenger RNAs and targeting incompletely synthesized protein fragments for degradation. Nuclear magnetic resonance (NMR) analysis of SmpB from Aquifex aeolicus revealed an antiparallel beta-barrel structure, with three helices packed outside the core of the barrel. While the overall structure of SmpB appears to be unique, the structure does contain an embedded oligonucleotide binding fold; in this respect SmpB has similarity to several other RNA-binding proteins that are known to be associated with translation, including IF1, ribosomal protein S17 and the N-terminal domain of aspartyl tRNA synthetase. Conserved amino acids on the protein surface that are most likely to directly interact with the tmRNA were identified. The presence of widely separated clusters of conserved amino acids suggests that SmpB could function either by stabilizing two distal regions of the tmRNA, or by facilitating an interaction between the tmRNA and another component of the translational apparatus. 相似文献
697.
Olejniczak M Gdaniec Z Fischer A Grabarkiewicz T Bielecki L Adamiak RW 《Nucleic acids research》2002,30(19):4241-4249
Binding of Mg2+, Ca2+ and Co(NH3)63+ ions to the HIV-1 TAR RNA in solution was analysed by 19F NMR spectroscopy, metal ion-induced RNA cleavages and Brownian dynamics (BD) simulations. Chemically synthesised 29mer oligoribonucleotides of the TAR sequence labelled with 5-fluorouridine (FU) were used for 19F NMR-monitored metal ion titration. The chemical shift changes of fluorine resonances FU-23, FU-25 and FU-40 upon titration with Mg2+ and Ca2+ ions indicated specific, although weak, binding at the bulge region with the dissociation constants (Kd) of 0.9 ± 0.6 and 2.7 ± 1.7 mM, respectively. Argininamide, inducing largest 19F chemical shifts changes at FU-23, was used as a reference ligand (Kd = 0.3 ± 0.1 mM). In the Pb2+-induced TAR RNA cleavage experiment, strong and selective cleavage of the C24-U25 phosphodiester bond was observed, while Mg2+ and Ca2+ induced cuts at all 3-nt residues of the bulge. The inhibition of Pb2+-specific TAR cleavage by di- and trivalent metal ions revealed a binding specificity [in the order Co(NH3)63+ > Mg2+ > Ca2+] at the bulge site. A BD simulation search of potential magnesium ion sites within the NMR structure of HIV-1 TAR RNA was conducted on a set of 20 conformers (PDB code 1ANR). For most cases, the bulge region was targeted by magnesium cations. 相似文献
698.
A protein complex containing Mdm10p,Mdm12p,and Mmm1p links mitochondrial membranes and DNA to the cytoskeleton-based segregation machinery
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Boldogh IR Nowakowski DW Yang HC Chung H Karmon S Royes P Pon LA 《Molecular biology of the cell》2003,14(11):4618-4627
Previous studies indicate that two proteins, Mmm1p and Mdm10p, are required to link mitochondria to the actin cytoskeleton of yeast and for actin-based control of mitochondrial movement, inheritance and morphology. Both proteins are integral mitochondrial outer membrane proteins. Mmm1p localizes to punctate structures in close proximity to mitochondrial DNA (mtDNA) nucleoids. We found that Mmm1p and Mdm10p exist in a complex with Mdm12p, another integral mitochondrial outer membrane protein required for mitochondrial morphology and inheritance. This interpretation is based on observations that 1) Mdm10p and Mdm12p showed the same localization as Mmm1p; 2) Mdm12p, like Mdm10p and Mmm1p, was required for mitochondrial motility; and 3) all three proteins coimmunoprecipitated with each other. Moreover, Mdm10p localized to mitochondria in the absence of the other subunits. In contrast, deletion of MMM1 resulted in mislocalization of Mdm12p, and deletion of MDM12 caused mislocalization of Mmm1p. Finally, we observed a reciprocal relationship between the Mdm10p/Mdm12p/Mmm1p complex and mtDNA. Deletion of any one of the subunits resulted in loss of mtDNA or defects in mtDNA nucleoid maintenance. Conversely, deletion of mtDNA affected mitochondrial motility: mitochondria in cells without mtDNA move 2-3 times faster than mitochondria in cells with mtDNA. These observations support a model in which the Mdm10p/Mdm12p/Mmm1p complex links the minimum heritable unit of mitochondria (mtDNA and mitochondrial outer and inner membranes) to the cytoskeletal system that drives transfer of that unit from mother to daughter cells. 相似文献
699.
Jaroszewski L Li W Godzik A 《Protein science : a publication of the Protein Society》2002,11(7):1702-1713
A major bottleneck in comparative modeling is the alignment quality; this is especially true for proteins whose distant relationships could be reliably recognized only by recent advances in fold recognition. The best algorithms excel in recognizing distant homologs but often produce incorrect alignments for over 50% of protein pairs in large fold-prediction benchmarks. The alignments obtained by sequence-sequence or sequence-structure matching algorithms differ significantly from the structural alignments. To study this problem, we developed a simplified method to explicitly enumerate all possible alignments for a pair of proteins. This allowed us to estimate the number of significantly different alignments for a given scoring method that score better than the structural alignment. Using several examples of distantly related proteins, we show that for standard sequence-sequence alignment methods, the number of significantly different alignments is usually large, often about 10(10) alternatives. This distance decreases when the alignment method is improved, but the number is still too large for the brute force enumeration approach. More effective strategies were needed, so we evaluated and compared two well-known approaches for searching the space of suboptimal alignments. We combined their best features and produced a hybrid method, which yielded alignments that surpassed the original alignments for about 50% of protein pairs with minimal computational effort. 相似文献
700.
Dodatko T Fedorov AA Grynberg M Patskovsky Y Rozwarski DA Jaroszewski L Aronoff-Spencer E Kondraskina E Irving T Godzik A Almo SC 《Biochemistry》2004,43(33):10628-10641
Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed beta-helix flanked by antiparallel beta-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface. This structural and biochemical characterization provides new insights into the organization and potential mechanistic properties of the multiprotein assemblies that integrate dynamic actin processes into the overall physiology of the cell. An unanticipated finding is that the unique tertiary structure of the C-CAP monomer provides a structural model for a wide range of molecules, including RP2 and cofactor C, proteins involved in X-linked retinitis pigmentosa and tubulin maturation, respectively, as well as several uncharacterized proteins that exhibit very diverse domain organizations. Thus, the unusual right-handed beta-helical fold present in C-CAP appears to support a wide range of biological functions. 相似文献