Enzyme residues

Enzyme residues in bold and larger font size. 

Enzyme residues in bold and larger font size. Substrate residues in plain text and smaller font size. Cleavage site nucleotide, Cl7, in a dashed box. Scissle C17-G1.1 phosphate bond marked with arrow. 

I was thinking particularly of electrostatic interactions between enzyme residues and substrate molecules. Let us compare the hydrophilic cytoplasmic phase (say, with dielectric constant e = 80) and the hydrophobic regions within membranes (say, with e = 2). Is it possible that protein-substrate interactions may be enhanced in certain membrane-associated enzyme schemes That is, might specific intermolecular forces play a more significant role in influencing the site-to-site migration of intermediate substrates, as compared to the same system in the hydrophilic phase [R. Coleman, Biochim. Biophys. Acta, 300, 1 (1973) P. A. Srere and K. Mosbach, Anti. Rev. Microbiol., 28, 61 (1974) and H. Frohlich, Proc. Nat. Acad. Sci. (U.S.), 72, 4211 (1975).]... 

If the main-chain hydrogen bonding of substrates is conserved among aspartic proteinases, how are the differences in specificities achieved Table 1 defines the enzyme residues that line the specificity pockets for both mouse and human renin. In modeling exercises (e.g., Reference 4) it was assumed that specificities derive from differences in the sizes of the residues in the specificity pockets (Sn) and their ability to complement the corresponding side chains at positions Pn in the substrate/inhibitor. A detailed analysis now shows that this simple assumption only partly accounts for the steric basis of specificity. 

Desolvation of the reacting polar groups is also a mechanism by which enzymes achieve rate accelerations. The desolvation of functional groups takes places during the inclusion of the reactants within the catalytic apparatus of the active site. This is another way of looking at the selective stabilization of the TS, in terms of a specific solvation of the reactants by the enzyme residues of the active site, which replaces the random solvation by the solvent molecules and the inherent enthalpic and entropic cost associated with their reorganization in the TS. 

Analysis of pseudorevertants (or suppressor) of unc mutants is a unique approach to find functional and/or structural interactions) between the two amino acid residues in the complex enzyme. Residues near the -y-phosphate moiety of ATP could be mapped relative to the residues in the glycine-rich sequence by identifying pseudorevertants of the mutants in the glycine-rich sequence. Conversely, other residues can also be mapped closely to the glycine-rich sequence, if effects of their mutations are suppressed by mutations in the glycine-rich sequence. 

Carboxyl-Terminal Extension of Class II Enzymes (Residues 126 to 134)... 

These experimental studies leave major aspects of the mechanism unresolved. The most important one is whether the catalysis proceeds via a general base mechanism or via a nucleophilic attack by an enzyme residue on the scissile bond. Although the experimental studies of carboxypeptidase A are providing essential information, they cannot show what species are actually involved in the reaction. For example, the suggestion that the zinc bound water acts as the nucleophile was based on the results of x-ray structures of unproductive and static complexes of carboxypeptidase A formed with pseudosubstrates and inhibitors (Christianson and Lipscomb 1985). 

Threonine 28 Proteasome enzymes Residue forms "OH from bound H20... 

Figure 12. Stereoview of the two binding modes found for 29 in the X-ray crystal structure with HIV-1 protease. The enzyme residues, Asp25/Aspl25 and ArglOS, are from the structure bound with the inhibitor conformer represented by the black lines.

Proposals for the detailed three-dimensional mechanism of UROS have been put forward [73, 74]. The mechanism really only requires one acidic group to protonate the HO group in the initial step and one basic group to perform the final deprotonation. It is possible that the same enzymic residue could perform both functions. Apart from this, the architecture of the active site must be such that, for the natural substrate 30, it favours the turning round of ring D and prevents the direct cychsation to give uro gen I. 

OR simulates the enzyme residue responsible for the enzyme-nucleotide interaction. 

---