Tight complex

The mode of action of the naphthoquinoid ansamacroHdes was estabHshed through studies using the tifamycins and streptovaricins (84,141,257,258). The ansamacroHdes inhibit bacterial growth by inhibiting RNA synthesis. This is accompHshed by forming a tight complex with DNA-dependent RNA polymerase. This complex is between the ansamacroHde and the P-unit of RNA polymerase. The formation of the complex inhibits the initation step of RNA synthesis (259,260). The ansamacroHdes form no such complex with mammalian RNA polymerase and thus have low mammalian toxicity. 

Serpins form very tight complexes with their corresponding serine pro-teinases, thereby inhibiting the latter. A flexible loop region of the serpin binds to the active site of the proteinases. Upon release of the serpin from the complex its polypeptide chain is cleaved by the proteinase in the middle of this loop region and the molecule is subsequently degraded. In addition to the active and cleaved states of the serpins there is also a latent state with an intact polypeptide chain that is functionally inactive and does not bind to the proteinase. 

In the absence of die polyether, potassium fluoride is insoluble in benzene and unreactive toward alkyl halides. Similar enhancement of solubility and reactivity of other salts is observed in the presence of crown ethers The solubility and reactivity enhancement result because the ionic compound is dissociated to a tightly complexed cation and a naked anion. Figure 4.13 shows the tight coordination that can be achieved with a typical crown ether. The complexed cation, because it is surrounded by the nonpolar crown ether, has high solubility in the nonpolar media. To maintain electroneutrality, the anion is also transported into the solvent. The cation is shielded from interaction with the anion as a... 

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... 

Derived from the German word meaning devil s copper, nickel is found predominantly in two isotopic forms, Ni (68% natural abundance) and Ni (26%). Ni exists in four oxidation states, 0, I, II, III, and IV. Ni(II), which is the most common oxidation state, has an ionic radius of —65 pm in the four-coordinate state and —80 pm in the octahedral low-spin state. The Ni(II) aqua cation exhibits a pAa of 9.9. It forms tight complexes with histidine (log Af = 15.9) and, among the first-row transition metals, is second only to Cu(II) in its ability to complex with acidic amino acids (log K( = 6-7 (7). Although Ni(II) is most common, the paramagnetic Ni(I) and Ni(III) states are also attainable. Ni(I), a (P metal, can exist only in the S = state, whereas Ni(lll), a cT ion, can be either S = or S =. ... 

A considerable explosion resulted from preparation of this compound (which presumably exists with several tightly complexed solvent molecules) in limited tetrahydrofuran under reflux. Investigation showed that there is an exotherm at 130°C, giving 440 J/g, followed by a more violent one at 300°C giving 690 J/g. Using a large excess of solvent no problems are observed. 

This 1,2-NH3 migration is the key step in the reorganization of the heavy atom skeleton which precedes pseudo-a-cleavage of ionized long-chain alkylamines (Scheme 3). The transition state for this process may be considered to resemble a tight complex of an ionized alkene (ethylene in the case of the archetypal /J-DI, CH2CH2NH3+) and NH3 (equation 9). This idea is consistent with the behaviour of adduct ions [C H2 NH3]+ generated by direct combination of the appropriate ionized alkene and NH3 58,59. 

Cardiolipin forms also tight complexes, with the adenine nucleotide translocator (ATM) affecting its translocator activity (Beyer and Nuscher, 1996). Six cardiohpin residues are tightly bound to lysines (Beyer and Klingenberg, 1985). Removal of these lipids renders the translocator inactive, but activity can be reconstituted by adding cardiolipin. It has also a pivotal role as a boundary hpid of various proteins such as NADH ubiquinone oxireductase (Hoch, 1992) or cytochrome c oxidase (Ushmorov et al, 1999 Vik et al, 1981). 

It is difficult to explain the rearrangement except by the indicated reaction steps. If these steps do occur, the propylene and HCo(CO)4 must be rather tightly complexed otherwise part or all of the volatile olefin would be lost. 

Carbonyl-substituted nitrones are formed as mixture of (E)- and (Z)-stereo-isomers. By coordination to a Lewis acid, the (Z)-isomers are expected to be more stabilized due to tight complexation. Thus, a 2.8 1 ( /Z)-mixture of A -(methoxy-carbonylmethylene)methylamine A -oxide isomerizes to the (Z)-isomer in the presence of MgBr2-Et20 and undergoes a regio- and exo-selective cycloaddition reaction to 2-propen-l-ol to give the isoxazolidine-5-methanol as a single product... 

There are two main routes for PS to interact with the target cell—it could form a tight complex with the surface receptors of the cell wall and /or could be transported inside the cell where it would associate with the molecule/organelle essential for survival. In the first case, the oxidative damage is localized on the cell wall, which could lead to its disintegration and the leakage of intracellular material, resulting in cell death. When the... 

The RNA polymerase of E. coli possesses with its subimit construction (a2PP o) a simple structure in comparison to eucaryotic RNA polymerases. The sigma factor is only required for the recognition of the promoter and the subsequent formation of a tight complex. After the incorporation of the first 8-10 nucleotides into the transcript, the sigma factor dissociates from the holoenzyme, and the remaining core enzyme carries out the rest of the elongation. 

In other families of E3 enzymes, no intermediate E3-ubiquitin linkage can be demonstrated. In this case ubiquitin is transferred directly from E2 to the substrate protein. The E3 enzymes are nevertheless required for ubiquitinylation since the E3 enzymes are responsible for substrate selection and are foimd in tight complexes with the cognate E2 proteins. 

Maximum stabilization occurs in the two-electron, two-orbital interaction. A system will reorient itself to maximize such an interaction. Figure 3.9 depicts the two most common instances of this interaction. Figure 3.9a may depict the interaction of a Lewis base with a Lewis acid to form a dative bond (e.g., NH3 + BF3 —> 1 +— ), a hydrogen bond, or a tight complex, as between aryl systems and NO+ [66]. The interaction... 

Fig. 4. Schematic representation of the observed dynamics. Initially uncomplexed photoacid first forms an encounter complex through diffusion. This loose complex either rearranges to a tight complex, or reacts via the hydrogen bonded network between photoacid and base. A pre-formed photoacid-base complex can directly react with extremely fast rates.

The statine residue mimics the noncovalently bonded tetrahedral intermediate, permitting formation of a very tight complex. Pepstatin is a poor inhibitor of human renin but its existence has inspired the synthesis of numerous related compounds, some of which are effective renin inhibitors/ Some of these inhibitors use the human angiotensinogen sequence with a secondary alcohol group mimicking the tetrahedral intermediate/ 2... 

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