Aspartate composite active site

Yamauchi et al.11121 concluded that aspartate racemase also uses two bases to remove and return the a-proton of the substrate. Aspartate racemase contains three cysteine residues Cys 84, Cys 190 and Cys 197, and only Cys 84 is essential for the enzyme activity. The alkylation of one cysteine residue/dimer with 2-nitro-5-thiocya-nobenzoic acid results in a complete loss of activity. Therefore, the enzyme shows a half-of-the-sites-reactivity11121. Yamauchi et al.11121 suggested that the enzyme has a composite active site formed at the interface of two identical subunits in the same manner as proposed for proline racemase1921. 

Stereoview of the polymerase active site of HIV-1 RT [38]. The amino acid residues that compose the putative dNTP-binding site, including the three catalytically essential aspartic acids, are shown with side chains. The double-stranded nucleic acid is shown with the atomic model in the HIV-1 RT/DNA/Fab complex. The dNTP-binding site consists of structural elements from both protein and nucleic acid. The precise composition, position, and conformation of the template-primer can affect the recognition of... 

To date, the composition of active sites is known for many enzymes, the most probable action mechanisms are suggested, and comparison data exist on catalytic group properties in enzymes and free molecules in solutions. Note also that the chemical composition of catalytic active sites of enzymes is independent of the presence of any specific compounds. Moreover, the majority of them are the well-known compounds for homogeneous catalysis histidine imidazole, carboxylic groups of aspartic and aminoglutaric acids, flavins, hemins, etc. However, as homogeneous catalysts, they possess rather moderate or even poor catalytic activity in appropriate reactions. 

The various serine proteases have similar primary shuctures, suggesting that they are evolutionarily related. They all have the same three catalyhc residues at the achve site an aspartate, a histidine, and a serine. But they have one important difference— the composition of the pocket at the active site that binds the side chain of the amino acid residue undergoing hydrolysis (Figure 24.6). This pocket is what gives the serine proteases their different specificities (Section 23.12). 

Describe the composition and arrangement of the subunits of ATCase and the major features of its active site as revealed by the binding o(N-(phosphonacetyl)-L-aspartate (PALA). Explain the effects of subunit dissociation on the allosteric behavior of the enzyme. 

NMD A receptors are selectively activated by A/-methyl-D-aspartate (NMD A) (182). NMD A receptor activation also requires glycine or other co-agonist occupation of an allosteric site. NMDAR-1, -2A, -2B, -2C, and -2D are the five NMD A receptor subunits known. Two forms of NMDAR-1 are generated by alternative splicing. NMDAR-1 proteins form homomeric ionotropic receptors in expression systems and may do so m situ in the CNS. Functional responses, however, are markedly augmented by co-expression of a NMDAR-2 and NMDAR-1 subunits. The kinetic and pharmacological properties of the NMD A receptor are influenced by the particular subunit composition. 

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