Histidine side chain

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 results of experiments in which the mutation was made were, however, a complete surprise. The Asp 189-Lys mutant was totally inactive with both Asp and Glu substrates. It was, as expected, also inactive toward Lys and Arg substrates. The mutant was, however, catalytically active with Phe and Tyr substrates, with the same low turnover number as wild-type trypsin. On the other hand, it showed a more than 5000-fold increase in kcat/f m with Leu substrates over wild type. The three-dimensional structure of this interesting mutant has not yet been determined, but the structure of a related mutant Asp 189-His shows the histidine side chain in an unexpected position, buried inside the protein. 

Alpha helices D and E from the L and M subunits (Figure 12.14) form the core of the membrane-spanning part of the complex. These four helices are tightly packed against each other in a way quite similar to the four-helix bundle motif in water-soluble proteins. Each of these four helices provides a histidine side chain as ligand to the Ee atom, which is located between the helices close to the cytoplasm. The role of the Ee atom is probably to... 

Each heme unit in myoglobin and hemoglobin contains one ion bound to four nitrogen donor atoms in a square planar arrangement. This leaves the metal with two axial coordination sites to bind other ligands. One of these sites is bound to a histidine side chain that holds the heme in the pocket of the protein. The other axial position is where reversible binding of molecular oxygen takes place. 

The structure of the enzymatic site of superoxide dismutase. The proximity, with a histidine side chain (color screened) acting as a bridge between the metals. 

Edgcomb SP, Murphy KP (2002) Variability in the pKa of histidine side-chains correlates with burial within proteins. Proteins 49 1-6. 

Equations (12.36) and (12.40) are the basis of the LRA method for calculating pi a shifts [59]. Indeed, to obtain the pKa shift due to the protein environment, we perform the same calculation for the protein and for a small molecule in solution, analogous to the side chain of interest. For a histidine side chain, for example, one would choose imidazole or methylimidazole in solution as a model compound. The pKa shift due to the protein environment will then have the form ... 

Protein functional groups able to react with anhydrides include the oc-amines at the N-terminals, the s-amine of lysine side chains, cysteine sulfhydryl groups, the phenolate ion of tyrosine residues, and the imidazolyl ring of histidines. However, acylation of cysteine, tyrosine, and histidine side chains forms unstable complexes that are easily reversible to regenerate the original group. Only amine functionalities of proteins are stable to acylation with anhydride reagents (Fraenkel-Conrat, 1959 Smyth, 1967). 

A sulfonyl chloride group rapidly reacts with amines in the pH range of 9-10 to form stable sulfonamide bonds. Under these conditions, it also may react with tyrosine —OH groups, aliphatic alcohols, thiols, and histidine side chains. Conjugates of sulfonyl chlorides with sulf-hydryls and imidazole rings are unstable, while esters formed with alcohols are subject to nucleophilic displacement (Nillson and Mosbach, 1984 Scouten and Van der Tweel, 1984). The only stable derivative with proteins therefore is the sulfonamide, formed by reaction with e-lysine... 

The addition of a radioactive iodine atom to a protein molecule typically has little effect on the resultant protein activity, unless the active center is modified in the process. The size of an iodine atom is relatively small and does not result in many steric problems with large molecules. The sites of potential protein modification are tyrosine and histidine side chains. Tyrosine may be modified with a total of two iodine atoms per phenolate group, whereas histidine can incorporate one iodine. Sulfhydryl modification at cysteine residues is typically unstable. 

Figure 12.5 IODO-GEN is a water-insoluble oxidizing agent that can react with 1251 - to form a highly reactive mixed halogen species, 125IC1. This intermediate can add radioactive iodine atoms to tyrosine or histidine side chain rings.

HRP C contains two different types of metal center (i.e., iron(III) protoporphyrin IX-heme group and two calcium atoms) that are fundamental for the integrity of the enzyme. The heme group is attached to the enzyme at His 170 by a coordinate bond between the histidine side-chain NE2 atom and the heme iron atom. The second axial coordination site is unoccupied in the resting state of the enzyme but available to hydrogen peroxide during enzyme turnover. Small molecules such as carbon monoxide, cyanide, fluoride, and azide bind to the heme iron atom at this distal site, giving six-coordinated PX complexes. 

AR Fletcher, JH Jones, WI Ramage, AV Stachulski. The use of the MJt)-phenacyl group for the protection of the histidine side chain in peptide synthesis. J Chem Soc Perkin Trans 1, 2261, 1979. 

T Brown, JH Jones, JD Richards. Further studies on the protection of histidine side chains in peptide synthesis use of the jr-benzyloxymethyl group. J Chem Soc Perkin Trans 1, 1553, 1982. 

For a pair of H-bonded histidine side chains, Ii3/Nn couplings in the range 8-11 Hz (Tab. 9.2) have been observed between a protonated 15Ne2-nucleus and an unprotonated 15Ne2 using an HNN-COSY-based technique [48]. These values are similar to the h2/NN coupling values observed for the imino and amino N-l I Nlorii ,, lc H-bonds of nucleic acid base pairs (Tab. 9.1). 

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