Charge relay chains

Golubev, N. S., Smirnov, S. N., Gindin, V. A., Denisov, G. S., Benedict, H., and Limbach, H.-H., Formation of charge relay chains between acetic acid and pyridine observed by low-temperature nuclear magnetic resonance, J. Am. Chem. Soc. 116, 12055-12056 (1994). 

G. Del Re H-Bond Charge-Relay Chains in Multi-Heme Cytochromes and Other Biomolecules. In Spectroscopy of Biological Molecules (C. Sandorfy and T. Theophanides, eds.), pp. 15-37. Dordrecht Reidel (1984). 

Spectroscopic methods can be used to specify the position of donors and acceptors before photoexcitation [50]. This spatial arrangement can obviously influence the equilibrium eomplexation in charge transfer complexes, and hence, the optical transitions accessible to such species [51]. This ordered environment also allows for effective separation of a sensitizing dye from the location of subsequent chemical reactions [52], For example, the efficiency of cis-trans isomerization of A -methyl-4-(p-styryl)pyridinium halides via electron transfer sensitization by Ru(bpy) + was markedly enhanced in the presence of anionic surfactants (about 100-fold) [53], The authors postulate the operation of an electron-relay chain on the anionic surface for the sensitization of ions attached electrostatically. High adsorptivity of the salt on the anionic micelle could also be adduced from salt effects [53, 54]. The micellar order also influenced the attainable electron transfer rates for intramolecular and intermolecular reactions of analogous molecules (pyrene-viologen and pyrene-ferrocene) solubilized within a cationic micelle because the difference in location of the solubilized substances affects the effective distance separating the units [55]. 

A type I thioesterase domain is present at the NHj-terminal of the animal FAS and is responsible for catalyzing hydrolysis of the completed fatty acyl chain from the enzyme. The active site contains both conserved serine and histidine residues [87] and is thought to function via a mechanism similar to that of the serine proteases [50] however, no conserved acidic residue is present to complete the charge relay/transfer. A second variety of thioesterase (type II) is encoded as a separate protein and interacts with the multifunctional FAS to release medium chain fatty acids [88, 89]. This enzyme has a weak sequence similarity to the type I thioesterase, which includes the conserved active site serine and histidine residues. These enzymes are also homologous to proteins encoded by genes involved in the synthesis of peptide antibiotics [90,91] (see below). 

FiGDRE 2.S3 Catalytic mechanism for hydrolysis of a peptide bond by chymotrypsin. fa) Four amino adds in the polypeptide chain of chymotrypsin have been shown ro participate in the chemLiitry of catalysis His S7, Asp 102, Gly 193, and Ser 195. (b Binding of the substrate a dietary polypeptide, to the active site of chymotrypsin. (c> The carbonyl group of the target peptide bond of the substrate becomes more polarized. (dl A charge relay... 

The presence of an ionized aspartic acid next to histidine raises its basicity and facilitates proton transfer from Ser-195 in the direction of His-57. If the proton resides on histidine, this side chain is positively charged. The charge is stabilized by the neighboring Asp-102, which may also stabilize the conformation of His-57. In some earlier proposals for SP mechanisms, it was assumed that a "double PT" or "charge relay" system is operating between the catalytic triad residues, and two PTs, the second being from His to Asp, take place. 

Figure 8.1. Conserved positions are often of functional importance. Alignment of trypsin proteins of mouse (SWISS-PROT P07146) and crayfish (SWISS-PROT P00765). Identical residues are underlined. Indicated above the alignments are three disulfide bonds (—s-s—), with participating cysteine residues conserved, amino acids side chains involved in the charge relay system (asterisk), and active side residue governing substrate specificity (diamond).

In the course of activation, chain segment 187-194 is rotated by 180°, bringing the catalytic amino acids to within 0.3 nm of the surface of the molecule. Substrate hydrolysis involves formation of an acyl-enzyme intermediate between the acid group of the peptide substrate and the hydroxyl of the Serjgs. The strongly nucleophilic character of this hydroxyl is due to the neighboring proton donor (or acceptor) His,. The effect is amplified by Asp Q (see Charge relay system). 

In the three-dimensional structure of chymotrypsin, the serine residue (which is residue 195 from the N-terminus of the chain and is hence termed serine-195) is located in close proximity to the residues histidine-57 and aspartate-102. The negatively charged aspartate-102 tends to withdraw a proton from the imidazole ring of histidine-57 adjacent to it. The imidazole ring then attracts a proton from serine-195. The effect of this charge relay system is to lower the effective pK of serine-195 and thus make it more reactive... 

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