Histidine Residue

The shape of a large protein is influenced by many factors including of course Its primary and secondary structure The disulfide bond shown m Figure 27 18 links Cys 138 of carboxypeptidase A to Cys 161 and contributes to the tertiary structure Car boxypeptidase A contains a Zn " ion which is essential to the catalytic activity of the enzyme and its presence influences the tertiary structure The Zn ion lies near the cen ter of the enzyme where it is coordinated to the imidazole nitrogens of two histidine residues (His 69 His 196) and to the carboxylate side chain of Glu 72... 

The imidazole nng of the histidine side chain acts as a proton acceptor in certain enzyme catalyzed reactions Which is the more stable protonated form of the histidine residue A or Why" ... 

The reaction between esterase and phosphorus inhibitor (109) is bimolecular, of the weU-known S 2 type, and represents the attack of a nucleophilic serine hydroxyl with a neighboring imida2ole ring of a histidine residue at the active site, on the electrophilic phosphorus atom, and mimics the normal three-step reaction that takes place between enzyme and substrate (reaction ). 

The world of zinc-containing DNA-binding proteins is by no means exhausted by these three subfamilies. Several other subfamilies are already known with different three-dimensional structures and different sequence patterns of cysteine and histidine residues that form the zinc ligands. Further subfamilies may well be discovered as the genomes of different species are sequenced whether or not any fundamentally new principles for DNA-protein recognition will be discovered amongst these new subfamilies remains to be seen. 

Figure 12.18 Ribbon diagram showing the a (red) and the P (blue) chains of the light-harvesting complex LH2. Each chain forms one transmembrane a helix, which contains a histidine residue that binds to the Mg atom of one bacteriochlorophyll molecule. (Adapted from G. McDermott et al.. Nature 374 517-521, 1995.)...

FIGURE 14.11 The pH activity profiles of four different enzymes. Trypsin, an intestinal protease, has a slightly alkaline pH optimnm, whereas pepsin, a gastric protease, acts in the acidic confines of the stomach and has a pH optimmn near 2. Papain, a protease found in papaya, is relatively insensitive to pHs between 4 and 8. Cholinesterase activity is pH-sensitive below pH 7 but not between pH 7 and 10. The cholinesterase pH activity profile suggests that an ionizable group with a pK near 6 is essential to its activity. Might it be a histidine residue within the active site ... 

FIGURE 19.24 A mechanism for the phosphoglycerate mutase reaction in rabbit muscle and in yeast. Zelda Rose of the Institute for Cancer Research in Philadelphia showed that the enzyme requires a small amount of 2,3-BPG to phosphorylate the histidine residue before the mechanism can proceed. Prior to her work, the role of the phosphohistidine in this mechanism was not understood. 

FIGURE 20.15 The covalent bond between FAD and succinate dehydrogenase involves the C-8a methylene group of FAD and the N-3 of a histidine residue on the enzyme. 

Complex II is perhaps better known by its other name—succinate dehydrogenase, the only TCA cycle enzyme that is an integral membrane protein in the inner mitochondrial membrane. This enzyme has a mass of approximately 100 to 140 kD and is composed of four subunits two Fe-S proteins of masses 70 kD and 27 kD, and two other peptides of masses 15 kD and 13 kD. Also known as flavoprotein 2 (FP2), it contains an FAD covalently bound to a histidine residue (see Figure 20.15), and three Fe-S centers a 4Fe-4S cluster, a 3Fe-4S cluster, and a 2Fe-2S cluster. When succinate is converted to fumarate in the TCA cycle, concomitant reduction of bound FAD to FADHg occurs in succinate dehydrogenase. This FADHg transfers its electrons immediately to Fe-S centers, which pass them on to UQ. Electron flow from succinate to UQ,... 

Electrons from cytochrome c are transferred to Cu sites and then passed to the heme iron of cytochrome a. Cu is liganded by two cysteines and two histidines (Figure 21.18). The heme of cytochrome a is liganded by imidazole rings of histidine residues (Figure 21.18). The Cu and the Fe of cytochrome a are within 1.5 nm of each other. 

Type 3 a pair of Cu atoms about 360 pm apart and attaehed to protein through histidine residues these effect O2 transport by means of the... 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Interestingly, however, the mechanisms of the two phosphate hydrolysis reactions in steps 9 and 11 are not the same. In step 9, water is the nucleophile, but in the glucose 6-phosphate reaction of step 11, a histidine residue on the enzyme attacks phosphorus, giving a phosphoryl enzyme intermediate that subsequently reacts with water. 

Histidine phosphatases and aspartate phosphatases are well established in lower organisms, mainly in bacteria and in context with two-component-systems . Reversible phosphorylation of histidine residues in vertebrates is in its infancy. The first protein histidine phosphatase (PHP) from mammalian origin was identified just recently. The soluble 14 kD protein does not resemble any of the other phosphatases. ATP-citrate lyase and the (3-subunit of heterotrimeric GTP-binding proteins are substrates of PHP thus touching both, metabolic pathways and signal transduction [4]. 

Klumpp S, Krieglstein J (2005) Reversible phosphorylation of histidine residues in vertebrate proteins. Minireview Biochim Biophys Acta 1754 291—295... 

A. A Simplified EVB Calculation of a Proton Transfer between Cysteine and Histidine in Water. (The reaction is represented in an oversimplified way by assigning all the histidine residual charges to a single nitrogen)... 

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