Proteins pKa values

Bas DC, Rogers DM, Jensen JH (2008) Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins 73 765-783. doi 10.1002/prot.22102 Li H, Robertson AD, Jensen JH (2005) Very fast empirical prediction and rationalization of protein pKa values. Proteins 61 704-721. doi 10.1002/prot. 20660 Olsson MH, Sondergaard CR, Rostkowski M, Jensen JH (2011) PROPKA3 consistent treatment of internal and surface residues in empirical pKa predictions. J Chem Theory Comput 7 525-537... 

Toseland, C.P., McSparron, H., Davies, M.N., Flower, D.R. PPD vl.O— An integrated, web-accessible database of experimentally determined protein pKa values. Nucleic Acids Res. 2006,34, D199-203. 

The structures, abbreviations (both three- and one-letter), and pKa values of the 20 amino acids commonly found in proteins are shown in Table 26.1. All are... 

Understanding the acidity and/or basicity of acids and bases in macrocyclic systems has an important connection to biological problems. It should help us to understand enzymes. In many proteins, drastically varying pKa values have been found for functional groups in the active site for example, the... 

Comparison of solution pH with the pKa of a side chain informs about the protonation state. A unique pKa, termed the standard or model pKa, can be experimentally determined for each ionizable side chain in solution when it is incorporated in a model compound, often a blocked amino acid residue [73] (Table 10-1). In a protein environment, however, the pKa value of an ionizable side chain can substantially deviate from the standard value, due to desolvation effects, hydrogen bonding, charge-charge, charge-dipole, and other electrostatic interactions with the... 

Table 10-1. Standard pKa values for titratable side chains in a protein [85, 97]...

Another interesting application area of PHMD simulations is to investigate electrostatic interactions in the unfolded states of proteins. A traditional view that unfolded proteins adopt random conformational states that are devoid of electrostatic and hydrophobic interactions, are recently challenged by experimental data [20, 69], REX-CPHMD folding simulations of the 35 residue C-terminal subdomain of the villin headpiece domain revealed a significant deviation from the standard pKa values for several titratable residues. Additional simulations, in which a charged group is neutralized confirmed the existence of specific electrostatic interactions in the unfolded states (JK and CLB, manuscript in preparation). 

Forsyth WR, Antosiewicz JM, Robertson AD (2002) Empirical relationships between protein structure and carboxyl pKa values in proteins. Proteins 48 388 103. 

Lee K, Fitch CA, Lecomte JT, Garcfa-Moreno EB (2002) Electrostatic effects in highly charged proteins Salt sensitivity of pKa values of histidines in staphylococcal nuclease. Biochemistry 41 5656-5667. 

The discovery of self-splicing introns showed that RNA could catalyse chemical reactions. Yet, unlike proteins, RNA has no functional groups with pKa values and chemical properties similar to those considered to be important in protein-based enzymes. Steitz and Steitz (1993) postulated that two metal ions were essential for catalysis by ribozymes using a mechanism similar to DNA cleavage, in which a free 3 OH is produced. They proposed,... 

Shaked, Z. Szajewski, R. R Whitesides, G. M. Rates of thiol-disulfide interchange reactions involving proteins and kinetic measurements of thiol pKa values. Biochemistry 1980,19,4156-4166. 

All amino acids have at least two ionizable groups, and their net charge therefore depends on the pH value. The COOH groups at the a-C atom have plmonocarboxylic acids. The basicity of the a-amino function also varies, with pKa values of between 8.8 and 10.6, depending on the amino acid. Acidic and basic amino acids have additional ionizable groups in their side chain. The plside chains are listed on p.60. The electrical charges of peptides and proteins are mainly determined by groups in the side chains, as most a-car-boxyl and a-amino functions are linked to peptide bonds (see p. 66). 

Why are the pKa values of different aspartie aeid side ehains in a protein not... 

Knowledge of the pKa value is crucial for analyzing both lipophilicity and solubility of ionizable compounds, as discussed above. Ionization equilibria also affect several toxicokinetic parameters, such as intestinal absorption, membrane permeability, protein binding, and metabolic transformations. Therefore, much research has been invested in developing both experimental and computational tools for pKa determination. Experimentally, two high-throughput methods exist spectral gradient analysis and capillary electrophoresis. However, the most definitive methods are still... 

Protamine sulphate (from herring sperm) [9007-31-2] (a]p -85.5 (satd H2O). A strongly basic protein (white powder) with pKa values of 7.4-8.0 used to ppte nucleic acids from crude protein extracts. It dissolved to the extent of 1.25% in H2O. It is freely soluble in hot H2O but separates as an oil on cooling. It has been purified by chromatography on an IRA-400 ion-exchange resin in the SO form and washed with dilute H2SO4. Eluates are freeze-dried under high vacuum below 20°. This method is used to convert proteamine and protamine hydrochloride to the sulphate. [UV Rasmussen Z physiol Chem 224 97 1934, Ando and Sawada J Biochem Tokyo 49 252 1961, Felix and Hashimoto Z physiol Chem 330 205 1963]... 

Buffers are often added to maintain a constant pH in biochemical research6 and naturally occurring buffer systems within body fluids and cells are very important (Box 6-A). Among the most important natural buffers are the proteins themselves, with the imidazole groups of histidine side chains providing much of the buffering capacity of cells around pH 7 (Figs. 3-1 and 3-2). Table 3-1 lists some useful biochemical buffers and their pKa values. Here are a few... 

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