Histidine units

Ribonuclease A is a member of a group of enzymes that cleave RNA using general acid-base catalysis without a metal ion in the enzyme. In ribonuclease A, such catalysis is performed by two imidazoles of histidine units, one as the free base (Im) and the other, protonated, as the acid (ImH+). To mimic this in an artificial enzyme, we prepared (3-cyclodextrin bis-imidazoles 41 [124]. The first one was a mixture of the... 

One major consequence of the basicity of imidazole is that at physiological pH (—7.4) substantial quantities of both the free base and protonated imidazole species are present in the histidine units of a protein. This allows histidine to act as either a proton acceptor or a proton donor according to the demands of its immediate environment. It seems likely that histidine units in a number of enzymes such as ribonuclease, aldolase and some proteases may have this role. The buffering action of histidine in the hemoglobin-oxyhemoglobin... 

Recently, de novo-synthesized four-helix polypeptides were applied to mimic functions of cytochrome b and to tailor layered cross-linked electrocatalytic electrodes. A four-helix bundle de novo protein (14728 Da) that includes four histidine units in the respective A -helices was assembled on Au electrodes (Figure 22A). Two units of Fe(III)-protoporphyrin IX were reconstituted into the assembly to yield a vectorial electron-transfer cascade [157]. The de novo-synthesized protein assembly forms affinity complexes with the cytochrome-dependent nitrate reductase (NR) and with Co(II) protoporphyrin IX-reconstituted myoglobin [158]. The resulting layered complex of Fe(III) de novo protein-NR or Fe(lll)-de novo protein-Co(II)-reconstituted myoglobin was cross-linked with glutaric dialdehyde to yield electrically contacted electrocatalytic electrodes. The Fe(lll)-de novo protein-NR electrode assembly was applied for the electrocatalyzed reduction NO3 to NOt" and acted as an amperometric sensor (Figure 22B). The Fe(III)-de novo... 

The basicity of imidazole was thoroughly covered in CHEC(1984) and CHEC-II(1996). The ambivalent acid-base properties of imidazole play an important role in the biochemical activity of the histidine unit. 

The high basicity of imidazole in comparison with other azoles has been attributed to the stability of the symmetrical imidazolium cation. That pyrazole is less basic can be ascribed to extra destabilization of the 7r-system on protonation <8iJHCl 189). Imidazole s pATj value of close to seven has ramifications for the biological activity of the histidine unit, for example, the two imidazole rings of His 12 and Hisl 19 in Ribonuclease A act as both acid and basic catalysts in the hydrolytic cleavage of RNA <91ACR317>. Some pK. values for substituted imidazoles are tabulated in Table... 

The iron in haemoglobin, the protein which carries oxygen in the blood, is bound in the centre of a planar porphyrin structure, referred to as protoporphyrin IX (Fig. 13.1). The compound of this porphyrin with iron is called haeme (ferroprotoporphyrin IX), and in the haemoglobin this unit is attached to the protein by the nitrogen of a histidine unit below the plane of... 

Quinidine, however, would appear to exhibit a certain degree of structural specificity with respect to its action on the heart [260, 861]. This action would seem to result from a binding to the cardiac cell membranes (possibly through interaction with histidine units [862, 863]) which inhibits the active transport of calcium ions into the cells [864] and so produces the characteristic reduction... 

Gastrin is an unusually strong acidic peptide with no basic amino acids and not less than 6 glutamic acid molecules and 1 aspartic acid amongst in total 17 amino acid units. Secretin is an extremely basic peptide with 27 amino acid units, amongst them 4 arginine units, 1 histidine unit and 2 of the 3 glutamic acid units y-amidated. No doubt, their electrokinetical properties are essential for their function. 

The first catalyst of this type to be reported by Miller et al. was a tripeptide, which adopted a 3-turn type structure with one intramolecular hydrogen bond. Interestingly, replacement of the alanine moiety by the more nucleophilic and less basic histidine unit resulted in higher selectivities in the KR of trons-... 

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