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The inserted side chain points directly toward the active site, where its negative charge may impede binding of β-lactams via repulsion against hydrophobic regions of the antibiotic or more simply alters the acylation chemistry that results in opening of the β-lactam ring by perturbing the electrostatic balance around the serine nucleophile.
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OLIGOs were designed using the MFOLD software (Genetics Computer Group, Madison), which provides the best RNA binding sites, and also takes into account the possibility of secondary structure folding that may facilitate or impede binding to sequences.
The two residues Val480 and Val484 are located in close proximity to the opening of the myosin binding canyon (Fig.S6E) and thus inserting two bulky and positively charged arginine residues at this position may impede substrate binding.
Methylation in CpG-rich regions within gene promoters is commonly associated with repressed gene expression, because it may impede the binding of transcription factors (Hashimshony et al. 2003).
The deposition of H3.3 at adjacent regions of RNA Pol II binding sites may impede Pol II or accommodate the binding of termination factors and result in short transcripts at enhancer elements and thereby ultimately define transcription end sites outside of genes.
Other reports suggest that p53-targeted genes may be downregulated by histone and promoter methylating enzyme recruitment in a p53-dependent manner, or that p53 may impede trans-activators from binding response elements within the promoters through protein protein interactions or by competing for DNA binding (Murphy et al, 1999).
As neutrophils are the predominant circulating leucocyte in septic shock, their decreased GR binding capacity may impede the response to exogenous or endogenous glucocorticoids.
Because thyroid binding globulin may impede the reliability of FT4 assays, it is preferable to use circulating total thyroxine as a measure of thyroid gland activity in pregnant women, because thyroid-binding globulin concentrations are elevated during pregnancy (Stagnaro-Green et al. 2011).
Constitutive expression of the HCV core or other DDX3-binding proteins may impede IFN induction and promote cell cycle progression.
However, the binding of mSOD1 to Hsp70 may impede Hsp70's normal antiapoptotic function, potentially promoting apoptosis and making the mitochondria more susceptible to stress [79].
On the basis of these two models, we hypothesized that binding of mecamylamine to the NL sites may impede the rotation of the M2 segments, disrupting the hydrophobic to polar residue switching, finally maintaining the receptor in a nonconducting conformation.
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