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121.
Rajesh Nair Jinfeng Liu Ta-Tsen Soong Thomas B. Acton John K. Everett Andrei Kouranov Andras Fiser Adam Godzik Lukasz Jaroszewski Christine Orengo Gaetano T. Montelione Burkhard Rost 《Journal of structural and functional genomics》2009,10(2):181-191
The Protein Structural Initiative (PSI) at the US National Institutes of Health (NIH) is funding four large-scale centers
for structural genomics (SG). These centers systematically target many large families without structural coverage, as well
as very large families with inadequate structural coverage. Here, we report a few simple metrics that demonstrate how successfully
these efforts optimize structural coverage: while the PSI-2 (2005-now) contributed more than 8% of all structures deposited
into the PDB, it contributed over 20% of all novel structures (i.e. structures for protein sequences with no structural representative
in the PDB on the date of deposition). The structural coverage of the protein universe represented by today’s UniProt (v12.8)
has increased linearly from 1992 to 2008; structural genomics has contributed significantly to the maintenance of this growth
rate. Success in increasing novel leverage (defined in Liu et al. in Nat Biotechnol 25:849–851, 2007) has resulted from systematic
targeting of large families. PSI’s per structure contribution to novel leverage was over 4-fold higher than that for non-PSI
structural biology efforts during the past 8 years. If the success of the PSI continues, it may just take another ~15 years
to cover most sequences in the current UniProt database. 相似文献
122.
Background
Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes.Methodology and Principal Findings
We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites.Conclusions and Significance
We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds. 相似文献123.
Background
Many ion channels are preferentially located in caveolae where compartmentalisation/scaffolding with signal transduction components regulates their activity. Channels that are mechanosensitive may be additionally dependent on caveolar control of the mechanical state of the membrane. Here we test which mechanism underlies caveolar-regulation of the mechanosensitive I Cl,swell channel in the adult cardiac myocyte.Methodology/Principal Findings
Rat ventricular myocytes were exposed to solution of 0.02 tonicity (T; until lysis), 0.64T for 10–15 min (swelling), and/or methyl-β-cyclodextrin (MBCD; to disrupt caveolae). MBCD and 0.64T swelling reduced the number of caveolae visualised by electron microscopy by 75 and 50% respectively. MBCD stimulated translocation of caveolin 3 from caveolae-enriched buoyant membrane fractions, but both caveolin 1 and 3 remained in buoyant fractions after swelling. I Cl,swell inhibition in control cells decreased time to half-maximal volume (t 0.5,vol; 0.64T), consistent with a role for I Cl,swell in volume regulation. MBCD-treated cells showed reduced time to lysis (0.02T) and t 0.5,vol (0.64T) compared with controls. The negative inotropic response to swelling (an index of I Cl,swell activation) was enhanced by MBCD.Conclusions/Significance
These data show that disrupting caveolae removes essential membrane reserves, which speeds swelling in hyposmotic conditions, and thereby promotes activation of I Cl,swell. They illustrate a general principle whereby caveolae as a membrane reserve limit increases in membrane tension during stretch/swelling thereby restricting mechanosensitive channel activation. 相似文献124.
Lifestyle‐determining extrachromosomal replicon pAMV1 and its contribution to the carbon metabolism of the methylotrophic bacterium Paracoccus aminovorans JCM 7685 下载免费PDF全文
125.
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling 总被引:2,自引:0,他引:2
Randall J. Platt Sidi Chen Yang Zhou Michael J. Yim Lukasz Swiech Hannah R. Kempton James E. Dahlman Oren Parnas Thomas M. Eisenhaure Marko Jovanovic Daniel B. Graham Siddharth Jhunjhunwala Matthias Heidenreich Ramnik J. Xavier Robert Langer Daniel G. Anderson Nir Hacohen Aviv Regev Guoping Feng Phillip A. Sharp Feng Zhang 《Cell》2014
126.
Lukasz Szatkowski Matthew K. Thompson Rafal Kaminski Stefan Franzen Agnieszka Dybala-Defratyka 《Archives of biochemistry and biophysics》2011,(1):22
The mechanism of the dehalogenation step catalyzed by dehaloperoxidase (DHP) from Amphitrite ornata, an unusual heme-containing protein with a globin fold and peroxidase activity, has remarkable similarity with that of the classical heme peroxidase, horseradish peroxidase (HRP). Based on quantum mechanical/molecular mechanical (QM/MM) modeling and experimentally determined chlorine kinetic isotope effects, we have concluded that two sequential one electron oxidations of the halogenated phenol substrate leads to a cationic intermediate that strongly resembles a Meisenheimer intermediate – a commonly formed reactive complex during nucleophilic aromatic substitution reactions especially in the case of arenes carrying electron withdrawing groups. 相似文献
127.
Szczepanska K Stanczuk L Maleszewski M 《Differentiation; research in biological diversity》2011,82(1):1-8
The ability of ICM to differentiate into TE is still a controversial issue. Many of authors have showed the reconstruction of TE from isolated ICMs. We showed that immunosurgical method is not 100% efficient and that the original TE cells very often remain on the surface of isolated ICMs. We also found that isolated ICM cells cultured in vitro do not express Cdx2, and that the TE is reconstituted from TE cells which have survived immunosurgery. This indicates that very soon after the formation of TE in the blastocyst, the cells of ICM lose the potency to differentiate into trophectoderm. 相似文献
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Kedarisetti KD Mizianty MJ Dick S Kurgan L 《Journal of bioinformatics and computational biology》2011,9(1):67-89
Accurate identification of strand residues aids prediction and analysis of numerous structural and functional aspects of proteins. We propose a sequence-based predictor, BETArPRED, which improves prediction of strand residues and β-strand segments. BETArPRED uses a novel design that accepts strand residues predicted by SSpro and predicts the remaining positions utilizing a logistic regression classifier with nine custom-designed features. These are derived from the primary sequence, the secondary structure (SS) predicted by SSpro, PSIPRED and SPINE, and residue depth as predicted by RDpred. Our features utilize certain local (window-based) patterns in the predicted SS and combine information about the predicted SS and residue depth. BETArPRED is evaluated on 432 sequences that share low identity with the training chains, and on the CASP8 dataset. We compare BETArPRED with seven modern SS predictors, and the top-performing automated structure predictor in CASP8, the ZHANG-server. BETArPRED provides statistically significant improvements over each of the SS predictors; it improves prediction of strand residues and β-strands, and it finds β-strands that were missed by the other methods. When compared with the ZHANG-server, we improve predictions of strand segments and predict more actual strand residues, while the other predictor achieves higher rate of correct strand residue predictions when under-predicting them. 相似文献