Line of evidence

Another line of evidence that bridging is important in the transition state for solvolysis has to do with substituent effects for groups placed at C-4, C-5, C-6, and C-7 on the norbomyl system. The solvolysis rate is most strongly affected by C-6 substituents, and the exo isomer is more sensitive to these substituents than is the endo isomer. This implies that the transition state for solvolysis is especially sensitive to C-6 substituents, as would be ejqiected if the C(l)—C(6) bond participates in solvolysis. ... 

Various lines of evidence indicate that ACh binds to the M1-M5 receptors within a cleft enclosed by the ring-like arrangement of TM I-VII, about 10-15 A away from the membrane surface [1, 3]. ACh binding induces as yet poorly understood changes in the arrangement of individual transmembrane helices. These conformational changes are then transmitted to the intracellular... 

The nature of the sulfur-oxygen bonds in sulfoxides and sulfones has been much discussed over many years. One would expect the actual structures to be intermediate between the canonical structures 3 and 6, and 8-11, respectively, and that discussion would be about the relative contributions of the various canonical structures. In practice the emphasis has been on the extremes is the sulfur-oxygen linkage in sulfoxides and sulfones essentially a coordinate bond or a double bond Various lines of evidence have been considered to bear on this question and these will now be examined briefly6. 

Thus three lines of evidence define the rapidly dissociating receptor as the LR complex. Conditions known to uncouple R from G--first, guanine nucleotide and second, pertussis toxin—produce LR third, reconstitution of G protein restores receptor affinity, sensitivity to guanine nucleotide, and effector activation. In this sense, the ligand and binding behavior of this system is analogous to that of the beta-adrenergic receptor, where the LR and LRG complexes have already been studied with purified proteins and reconstituted membrane preparations (2,i0). 

Fig. 8. A model for the catalytic cycle of hydrodenase based on several lines of evidence (see text).

The lack of structural similarity between a feedback inhibitor and the substrate for the enzyme whose activity it regulates suggests that these effectors are not isosteric with a substrate but allosteric ( occupy another space ). Jacques Monod therefore proposed the existence of allosteric sites that are physically distinct from the catalytic site. Allosteric enzymes thus are those whose activity at the active site may be modulated by the presence of effectors at an allosteric site. This hypothesis has been confirmed by many lines of evidence, including x-ray crystallography and site-directed mutagenesis, demonstrating the existence of spatially distinct active and allosteric sites on a variety of enzymes. 

This would accomplish substitution of Y for X by a potentially associative solvent attack followed by a fast replacement of solvent. This interpretation of the ki path is strongly supported by two lines of evidence. 

Up to now, the pectinolytic enzymes of E. chrysanthemi that have been detected were extracellular secreted enzymes (PelA, B, C, D, E, L, exo-Peh and PemA), periplasmic (exo-Pel), or cytoplasmic (OGL) proteins (1, 5). In contrast, PemB is an outer membrane pectinolytic enzyme. To our knowledge it is the first pectinase characterised as a membrane protein. We presented several lines of evidence showing that PemB is a lipoprotein (i) Its N-terminal sequence has the characteristics of lipoprotein signal sequences, (ii) PemB is synthesised as a high molecular weight precursor processed into a lower molecular weight mature form, (iii) Palmitate, the most prevalent fatty acid in bacterial lipoproteins (12), is incorporated into PemB. 

The most straight-forward interpretation of the phosphorylation reaction would be that exactly the same reaction is catalyzed as during transport of the sugar into the cell where the substrate is offered to the periplasmic side of the membrane (Eq. (1), overall reaction) phosphorylation would measure transport as well. However, this may not be the case several lines of evidence discussed in the previous sections indicate that the mechanism underlying the phosphorylation reaction could be much more complex. Factors that may complicate the interpretation of the phosphorylation reaction in detergent solutions are ... 

L-type Ca channels are primarily regulated by voltage and are thus opened and closed in response to changes in membrane potential, but in addition, they are regulated by receptor-dependent processes involving protein phosphorylation and G-proteins (Fig. 2). Many lines of evidence support the hypothesis that Ca channels are regulated by phosphorylation by several protein kinases, in particular by... 

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