Amino add side chains

Figure 3.1 Amino add side-chain groups involved in binding NAD at the active site of an enzyme. The enzyme is glyceraldehyde dehydrogenase. More than 20 amino acids, the position of which in the primary structure is indicated by the number, counting from the N-terminal amino acid, are involved in the binding. This emphasises the complexity of the binding that is responsible for the specificity of the enzyme for NAD (depicted in bold). The molecular structure of nicotinamide adenine dinucleotide (NAD ) provided in Appendix 3.3.

Fig. 1.5. Zif268 in complex with DNA. a) specific H-bonds between amino add side chains of fingers 1-3 of Zif268 and bases of the recognition sequence. The DNA is drawn as cylinders. The arrows emphasize contact with the major groove, b) periodic arrangement of fingers in the major groove of the DNA. According Pabo and Sauer (1992), with permission.

Table 2 contains some examples of TTN oxidative coupling reactions. These examples show that the reaction can often tolerate unprotected amino add side chains, and that both 14- and 17-membered cycloisodityrosines can be obtained. In addition, the TTN oxidative coupling has been employed in the formation of 16-membered cyclic biaryl ethers of the type found in vancomycinJ20,21 The drawbacks of TTN oxidative coupling are the low yields, the formation of byproducts, and the need for additional transformations to arrive at the cycloisodityrosine target. 

X Sugars, amino add side chains, ribonucleic acid... 

Hydration of amino add side-chain and polypeptide main-chain atoms. In Thble 23.4, the hydration of the 15 well-refined proteins given in Thble 19.1 is analyzed in terms of functional groups in main-chains and in side-chains. About 44% of the water molecules are bound to side-chain atoms, 42% to main-chain C=0 and only 14% to main-chain N-H. 

Figure 1. Types of antigenic determinants. An assembled epitope is composed of amino acid side chains (1,2, and 3) that are well separated in the linear sequence of the protein but are brought together during folding of the protein. A segmental epitope is composed of amino add side chains (A, B, and C) that are contiguous both in the linear sequence of the protein and on the surface of the protein in its folded form.

Jackson DE, Poncz M, Holyst MT, Newman PJ Inherited mutations within the addum-binding sites of the integrin allb subunit (platelet glycoprotdn lib). Effects of the amino add side chain and the amino add position on cation binding. Eur J Biochem 240 280-287,19%. 

A central and widely used tool for membrane anchoring is the post-translational attachment of hydrophobic residues, such as fatty adds, isoprenoids (see Fig. 3.12) or complex glycolipids (see Fig. 31.15) to spedfic amino add side chains of target proteins. These lipid moieties of lipidated proteins favor membrane assodation by increasing the affinity of the protein to the membrane. Because of their hydrophobic nature, the membrane anchors insert into the phospholipid bilayer and thus mediate... 

Figure 2.2 Modem solid phase peptide synthesis (Contd.). Most frequently used amino add side chain protecting groups are shown t-BOC tert-bulyloxycarbonyl Trt trityl PMC 2,2,5,7,8-pentamethylchroman-6-sulphonyl PBF 2,2,4,6,7-pentamethyl-dihydrobenzofuran-5-sulphonyl.

More recently an oil continuous microemulsion technique has been described, which allows the study of specific interactions between amino add side chains and metal ions. Both the metal ion and amino acid are microencapsulated as aqueous droplets in a dispersed phase. The technique is of particular relevance to metalloprotein and metal-membrane interactions where the local dielectric constant can be considerably less than that of bulk water. 

MacCallum, J.L., Bennett, W.F.D., Tieleman, D.P Partitioning of amino add side chains into Hpid bilayers Results from computer simulaHons and comparison to experiment. J. General Phys. 2007, 129,371-7. 

Deng, Y., Roux, B. Hydration of amino add side chains Nonpolar and electrostatic contributions calculated from staged molecular dynamics free energy simulations with explicit water molecules, J. Chem. Phys. 2004,108,16567-76. 

MaccaUum, J.L., Heleman, D.P. Calculation of the water-cyclohexane transfer free energies of neutral amino add side-chain analogs using the OPLS aU-atom force field, J. Comp. Chem. 2003, 24(15), 1930-5. 

Xu, Z., Luo, H.H., Tieleman, D.P. Modifying the OPLS-AA force field to improve hydration free energies for several amino add side chains using new atomic charges and an off-plane charge model for aromatic residues, J. Comp. Chem. 2007,28, 689-97. 

The role of FAD in the AHAS reaction is not fully understood since no oxidation or reduction occurs. Several hypotheses have been put forth, but so far no experimental evidence has conclusively supported any single explanation. One possibility is that FAD plays a structural role only and is likely an evolutionary remnant from a pyruvate oxidase (POX)-like ancestor [14]. The divalent metal ion does not play a direct role in the reaction, but serves to anchor the ThDP molecule to the protein by coordinating the diphosphate group and certain amino add side chains [15]. 

Breaking cystine residue disulfide cross-links [13], or breaking peptide bonds in the protein main-chains, increases the equilibrium water content of wool at RHs above 80%. Acetylation of amino and hydroxyl groups, or esterification of carboxylic add groups in amino add side-chains, decreases the EWC of wool at low RHs because each treatment replaces hydrophilic groups with less hydrophilic groups. 

Table 1. Amino add side chains and their functions ...

In the particular case of alcohol dehydrogenase, outlined in Section 15.3, the combination of temperature studies with solvent perturbation will separate the neutral amino acids from the cationic ones, provided the group is ejqiosed to the solvent. Thus, by combining the knowledge of pK and the heat of ionization for a given amino add side chain with a solvent perturbation method, a fairly accurate identification of an amino acid can be achieved. 

Assign charges to amino add side chains. The active site residue protonation state is important and can have a significant effect on binding affinity. The protonation states of amino acid residues such as His, Lys, Glu, and Asp are usually based on their pX values but can be influenced by neighboring donor-acceptor groups. 

The electron density map obtained from the analysis of methemerythrin allowed the location of most amino-add side chains in the protein and the confirmation of His-25, His-54, Glu-58, His-73, His-77, His-101, Asp-106, and Tyr-109 as the iron-ligands. The residues involved in the association of the subunits to form the octamer could also be identified. 

Figure 16 Comparisons of the hydration free energies of amino-add side chain analogs predicted from 3D-SDFT to both the simuiation resuits and the avaiiabie experimental measurements. After Liu et at. (2013a).

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