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Hemoglobin (Hb), an oxygen‐binding protein composed of four subunits (α1, α2, β1, and β2), is a well‐known example of allosteric proteins that are capable of cooperative ligand binding. Despite decades of studies, the structural basis of its cooperativity remains controversial. In this study, we have integrated coarse‐grained (CG) modeling, all‐atom simulation, and structural data from X‐ray crystallography and wide‐angle X‐ray scattering (WAXS), aiming to probe dynamic properties of the two structural states of Hb (T and R state) and the transitions between them. First, by analyzing the WAXS data of unliganded and liganded Hb, we have found that the structural ensemble of T or R state is dominated by one crystal structure of Hb with small contributions from other crystal structures of Hb. Second, we have used normal mode analysis to identify two distinct quaternary rotations between the α1β1 and α2β2 dimer, which drive the transitions between T and R state. We have also identified the hot‐spot residues whose mutations are predicted to greatly change these quaternary motions. Third, we have generated a CG transition pathway between T and R state, which predicts a clear order of quaternary and tertiary changes involving α and β subunits in Hb. Fourth, we have used the accelerated molecular dynamics to perform an all‐atom simulation starting from the T state of Hb, and we have observed a transition toward the R state of Hb. Further analysis of crystal structural data and the all‐atom simulation trajectory has corroborated the order of quaternary and tertiary changes predicted by CG modeling. Proteins 2013. © 2012 Wiley Periodicals, Inc. 相似文献
84.
Abstract We present a “force-biased” algorithm for generating the irregular close packing of hard spheres. The algorithm is partly based on Jodrey and Tory's ideas [9] and incorporates methods from Molecular Dynamics. Packings generated by means of the two algorithms are consistent up to final packing fraction of 0.65, which seems to be the limit density of Jodrey and Tory's method. Significantly higher densities (up to 0.71) can be achieved for small numbers of spheres by the force-biased algorithm. However the shape of the radial and angle distribution functions implies that a partial short-range ordering occurs in packings of those densities. 相似文献
85.
Lixia Yu Qiuxia Lin Jianhua Feng Xiaohong Dong Wenjun Chen Qifeng Liu Jianming Ye 《Cellular signalling》2013,25(3):581-588
It has been demonstrated that nephrin inactivation plays a critical role in Angiotensin II (AngII)-induced podocyte damage both in in vitro and in vivo, but the underlying molecular mechanisms are still unclear. Recently, c-maf inducing protein (c-mip) has been identified as a key component in the molecular pathogenesis of acquired podocyte diseases. In this study, the role of c-mip on AngII-induced nephrin inactivation and podocyte damage was explored in a mouse podocyte cell line. AngII stimulation caused podocyte damage, presenting with a time and dose dependent cell apoptosis increment, and obvious reorganization of actin cytoskeleton, both of which was remarkably prevented by knockdown of c-mip (siCmip). In AngII stimulated podocyte, c-mip and Csk expressions increased obviously at protein level, and nephrin phosphorylation decreased while Cbp phosphorylation increased. AngII-induced Csk increment and nephrin inactivation was remarkably inhibited by siCmip treatment. AngII stimulation increased the interaction of c-mip and Csk, as well as Csk and Cbp. Notably, the binding of Csk to active form pY418 decreased while the binding of Csk to inactive form pY530 of Src kinase Fyn increased in AngII-stimulated podocyte. Nevertheless, c-mip knockdown prevented AngII-induced reduction of pY418 and increase of pY530. In addition, AngII stimulation significantly decreased the expression of phosphor-Akt (Ser473) and antiapoptotic protein Bcl-2, whereas increased the expression of apoptotic proteins caspase-3 and BAD, all of which were prevented by siCmip treatment. Taken together, our results demonstrated that AngII induced nephrin inactivation and podocyte damage by the novel podocyte protein c-mip through Csk–Cbp–Fyn signaling pathway. 相似文献
86.
Several chiral ligands containing (R,R)‐diaminocyclohexane moieties and pyrrole, furan, or benzene have been synthesized. These ligands were tested in enantioselective zinc‐catalyzed hydrosilylation reactions; excellent enantioselectivities were obtained when the ligands containing (R,R)‐diaminocyclohexane moieties and furan rings were used. For comparison, zinc chloride combined with different potassium carboxylate salts and ligands were also tested for catalytic hydrosilylation reactions. Chirality 25:275–280, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
87.
Degradation kinetics of biochar from pyrolysis and hydrothermal carbonization in temperate soils 总被引:2,自引:0,他引:2
Mo Bai Burkhard Wilske Franz Buegger Jürgen Esperschütz Claudia Irene Kammann Christian Eckhardt Martin Koestler Philipp Kraft Martin Bach Hans-Georg Frede Lutz Breuer 《Plant and Soil》2013,372(1-2):375-387
Background and Aims
Estimates of biochar residence times in soils range over three orders of magnitude. We present the first direct comparison between the biodegradation of a char from hydrothermal carbonization (htcBC) and pyrolysis (pyrBC) with high temporal resolution.Methods
Mineralization of the biochars and their shared Miscanthus feedstock in three soils was determined directly by the 13CO2 efflux using a novel method incorporating wavelength scanned cavity ring-down spectroscopy. Biochar half-life (t1/2) was estimated with three empirical models.Results
(1) The htcBC was readily biodegradable, whereas pyrBC was more recalcitrant. (2) Cumulative degradation of both biochars increased with soil organic carbon and nitrogen content. (3) The corrected Akaike information criterion (AICC) showed an overall preference for the double exponential model (DEM) reflecting a labile and a recalcitrant C-pool, over the first-order degradation model (FODM) and a logarithmic model. (4) The DEM resulted in t1/2 ranging from 19.7–44.5, 0.7–2.1 and 0.8–1.3 years for pyrBC, htcBC and feedstock, respectively.Conclusion
The degradation was rather similar between feedstock and htcBC but one order of magnitude slower for pyrBC. The AICC preferred FODM in two cases, where the DEM parameters indicated no distinction between a labile and recalcitrant carbon pool. 相似文献88.
Wei Wei Wenjun Zhu Jiasen Cheng Jiatao Xie Bo Li Daohong Jiang Guoqing Li Xianhong Yi Yanping Fu 《Applied and environmental microbiology》2013,79(12):3658-3666
Coniothyrium minitans is a sclerotial parasite of the plant-pathogenic fungus Sclerotinia sclerotiorum, and conidial production and parasitism are two important aspects for commercialization of this biological control agent. To understand the mechanism of conidiation and parasitism at the molecular level, we constructed a transfer DNA (tDNA) insertional library with the wild-type strain ZS-1. A conidiation-deficient mutant, ZS-1TN22803, was uncovered through screening of this library. This mutant could produce pycnidia on potato dextrose agar (PDA), but most were immature and did not bear conidia. Moreover, this mutant lost the ability to parasitize or rot the sclerotia of S. sclerotiorum. Analysis of the tDNA flanking sequences revealed that a peroxisome biogenesis factor 6 (PEX6) homolog of Saccharomyces cerevisiae, named CmPEX6, was disrupted by the tDNA insertion in this mutant. Targeted gene replacement and gene complementation tests confirmed that a null mutation of CmPEX6 was responsible for the phenotype of ZS-1TN22803. Further analysis showed that both ZS-1TN22803 and the targeted replacement mutants could not grow on PDA medium containing oleic acid, and they produced much less nitric oxide (NO) and hydrogen peroxide (H2O2) than wild-type strain ZS-1. The conidiation of ZS-1TN22803 was partially restored by adding acetyl-CoA or glyoxylic acid to the growth media. Our results suggest that fatty acid β-oxidation, reactive oxygen and nitrogen species, and possibly other unknown pathways in peroxisomes are involved in conidiation and parasitism by C. minitans. 相似文献
89.
Yang Wang Wenjun Shang Xia Lei Shukun Shen Hongxin Zhang Zhugang Wang Lei Huang Zhiwei Yu Huishan Ong Xuelai Yin Wenjun Yang Chenping Zhang 《Biotechnology letters》2013,35(9):1377-1385
Over-expression of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1) plays a crucial role in the formation of pleomorphic adenoma, which is the most common type of salivary gland tumor. To understand the molecular mechanisms governing PLAG1-mediated tumorigenesis, we used a microarray-based approach to identify PLAG1 target genes. We validated the expression of several genes, including Bax, Fas, p53, p21, p16, Cyclin D1, Egfr, Trail-R/DR5, c-Fos, c-myc and Igf2, by real-time RT-PCR or western blotting. Using luciferase reporter gene assays, we determined that the promoters of Bax, Fas, p53, TRAIL-R/DR5, and c-Fos were transactivated by PLAG1. PLAG1 not only activates genes that promote cell proliferation and tumor formation but also genes that inhibit these cellular processes. Therefore, we conclude that PLAG1 may play a dual role in tumor formation. 相似文献