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排序方式: 共有123条查询结果,搜索用时 452 毫秒
101.
Lavanyaa Manjunath David Coombes James Davies Mugdha Dhurandhar Vikas R. Tiwari Renwick C. J. Dobson R. Sowdhamini S. Ramaswamy Sucharita Bose 《Proteins》2021,89(1):81-93
N‐acetylglucosamine 6‐phosphate deacetylase (NagA) catalyzes the conversion of N‐acetylglucosamine‐6‐phosphate to glucosamine‐6‐phosphate in amino sugar catabolism. This conversion is an essential step in the catabolism of sialic acid in several pathogenic bacteria, including Pasteurella multocida, and thus NagA is identified as a potential drug target. Here, we report the unique structural features of NagA from P. multocida (PmNagA) resolved to 1.95 Å. PmNagA displays an altered quaternary architecture with unique interface interactions compared to its close homolog, the Escherichia coli NagA (EcNagA). We confirmed that the altered quaternary structure is not a crystallographic artifact using single particle electron cryo‐microscopy. Analysis of the determined crystal structure reveals a set of hot‐spot residues involved in novel interactions at the dimer‐dimer interface. PmNagA binds to one Zn2+ ion in the active site and demonstrates kinetic parameters comparable to other bacterial homologs. Kinetic studies reveal that at high substrate concentrations (~10‐fold the KM), the tetrameric PmNagA displays hysteresis similar to its distant neighbor, the dimeric Staphylococcus aureus NagA (SaNagA). Our findings provide key information on structural and functional properties of NagA in P. multocida that could be utilized to design novel antibacterials. 相似文献
102.
Mugdha Deshpande Fakhriddin Pirlepesov Thierry Lints 《Proceedings. Biological sciences / The Royal Society》2014,281(1781)
As in human infant speech development, vocal imitation in songbirds involves sensory acquisition and memorization of adult-produced vocal signals, followed by a protracted phase of vocal motor practice. The internal model of adult tutor song in the juvenile male brain, termed ‘the template’, is central to the vocal imitation process. However, even the most fundamental aspects of the template, such as when, where and how it is encoded in the brain, remain poorly understood. A major impediment to progress is that current studies of songbird vocal learning use protracted tutoring over days, weeks or months, complicating dissection of the template encoding process. Here, we take the key step of tightly constraining the timing of template acquisition. We show that, in the zebra finch, template encoding can be time locked to, on average, a 2 h period of juvenile life and based on just 75 s of cumulative tutor song exposure. Crucially, we find that vocal changes occurring on the day of training correlate with eventual imitative success. This paradigm will lead to insights on how the template is instantiated in the songbird brain, with general implications for deciphering how internal models are formed to guide learning of complex social behaviours. 相似文献
103.
Staurosporine was found to bring about complete growth inhibition of human glioma cell lines. U87 MG cells were arrested in S phase while U373 MG cells in G2/M phase on staurosporine treatment. Consistent with this observation, no change in G1 phase regulators viz., Cyclin D1, D3 and CDK4 was seen on staurosporine treatment. The levels of CDK2, CDC2, Cyclin A and Cyclin B proteins decreased, while the levels of CDK inhibitors viz., p21 and p27 were found to increase on staurosporine treatment. The mRNA levels of CDK2 and CDC2 genes were also found to decrease on staurosporine treatment. Thus apart from staurosporine’s known direct inhibitory effect on CDK2 and CDC2 activities, staurosporine was found to down-regulate activities of these two kinases by modulating the expression of the kinases themselves as well that of their activating partners (Cyclins) and their inhibitors. 相似文献
104.
Chetan J. Gadgil 《Bulletin of mathematical biology》2009,71(7):1599-1611
In this paper, it is shown that for a class of reaction networks, the discrete stochastic nature of the reacting species and
reactions results in qualitative and quantitative differences between the mean of exact stochastic simulations and the prediction
of the corresponding deterministic system. The differences are independent of the number of molecules of each species in the
system under consideration. These reaction networks are open systems of chemical reactions with no zero-order reaction rates.
They are characterized by at least two stationary points, one of which is a nonzero stable point, and one unstable trivial
solution (stability based on a linear stability analysis of the deterministic system). Starting from a nonzero initial condition,
the deterministic system never reaches the zero stationary point due to its unstable nature. In contrast, the result presented
here proves that this zero-state is a stable stationary state for the discrete stochastic system, and other finite states
have zero probability of existence at large times. This result generalizes previous theoretical studies and simulations of
specific systems and provides a theoretical basis for analyzing a class of systems that exhibit such inconsistent behavior.
This result has implications in the simulation of infection, apoptosis, and population kinetics, as it can be shown that for
certain models the stochastic simulations will always yield different predictions for the mean behavior than the deterministic
simulations. 相似文献
105.
Gadgil S 《Journal of mathematical biology》2009,59(1):123-142
We study the secondary structure of RNA determined by Watson–Crick pairing without pseudo-knots using Milnor invariants of
links. We focus on the first non-trivial invariant, which we call the Heisenberg invariant. The Heisenberg invariant, which
is an integer, can be interpreted in terms of the Heisenberg group as well as in terms of lattice paths. We show that the
Heisenberg invariant gives a lower bound on the number of unpaired bases in an RNA secondary structure. We also show that
the Heisenberg invariant can predict allosteric structures for RNA. Namely, if the Heisenberg invariant is large, then there are widely separated local maxima (i.e., allosteric structures)
for the number of Watson–Crick pairs found.
Partially supported by DST (under grant DSTO773) and UGC (under SAP-DSA Phase IV). 相似文献
106.
Gadgil M 《Trends in ecology & evolution》1987,2(12):369-373
Early human populations utilized a wide range of biological resources in a tremendous diversity of environments. As a result, they possessed high levels of cultural diversity dependent on and supportive of high levels of biological diversity. This pattern changed drastically with technological innovations enabling certain human groups to break down territorial barriers and to usurp resources of other groups. The dominant groups have gone on to exhaust a whole range of resources, depleting both biological and cultural diversity. Traditions of resource conservation can, however, re-emerge when the dominant cultures spread over the entire area and the innovations diffuse to other human groups. This could change once again as genetically engineered organisms become an economically viable proposition with the accruing advantages concentrated in the hands of a few human groups: a further drastic reduction in biological and cultural diversity may ensue. 相似文献
107.
Most U-rich small nuclear ribonucleoproteins (snRNPs) are complexes that mediate the splicing of pre-mRNAs. U7 snRNP is an exception in that it is not involved in splicing but is a key factor in the unique 3′ end processing of replication-dependent histone mRNAs. However, by introducing controlled changes in the U7 snRNA histone binding sequence and in the Sm motif, it can be used as an effective tool for gene therapy. The modified U7 snRNP (U7 Sm OPT) is thus not involved in the processing of replication-dependent histone pre-mRNA but targets splicing by inducing efficient skipping or inclusion of selected exons. U7 Sm OPT is of therapeutic importance in diseases that are an outcome of splicing defects, such as myotonic dystrophy, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, β-thalassemia, HIV-1 infection and spinal muscular atrophy. The benefits of using U7 Sm OPT for gene therapy are its compact size, ability to accumulate in the nucleus without causing any toxic effects in the cells, and no immunoreactivity. The risk of transgene misregulation by using U7 Sm OPT is also low because it is involved in correcting the expression of an endogenous gene controlled by its own regulatory elements. Altogether, using U7 Sm OPT as a tool in gene therapy can ensure lifelong treatment, whereas an oligonucleotide or other drug/compound would require repeated administration. It would thus be strategic to harness these unique properties of U7 snRNP and deploy it as a tool in gene therapy. 相似文献
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