Enzymes conserved group

An enzyme nucleophilic group, most likely SH in the context of the Pro-Cys doublet conserved in all known m C-MTases, is believed to assist the chemical catalysis by attacking the C-6 of the substrate cytosine. Formation of a covalent intermediate apparently renders the otherwise inert C-5 electron rich and facilitates the electrophilic transfer of a methyl group from AdoMet. In the absence of AdoMet, M Hhal catalyzes the exchange of the 5-H of the substrate cytosine for protons of water at a rate about sevenfold higher than the rate of methylation. 

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

Tlie Na+/K+-ATPase belongs to the P-type ATPases, a family of more than 50 enzymes that also includes the Ca2+-ATPase of the sarcoplasmic reticulum or the gastric H+/K+-ATPase. P-Type ATPases have in common that during ion transport an aspartyl phos-phointermediate is formed by transfer of the y-phosphate group of ATP to the highly conserved sequence DKTGS/T [1]. 

The antibiotic activity of certain (3-lactams depends largely on their interaction with two different groups of bacterial enzymes. (3-Lactams, like the penicillins and cephalosporins, inhibit the DD-peptidases/transpeptidases that are responsible for the final step of bacterial cell wall biosynthesis.63 Unfortunately, they are themselves destroyed by the [3-lactamases,64 which thereby provide much of the resistance to these antibiotics. Class A, C, and D [3-lactamases and DD-peptidases all have a conserved serine residue in the active site whose hydroxyl group is the primary nucleophile that attacks the substrate carbonyl. Catalysis in both cases involves a double-displacement reaction with the transient formation of an acyl-enzyme intermediate. The major distinction between [3-lactamases and their evolutionary parents the DD-peptidase residues is the lifetime of the acyl-enzyme it is short in (3-lactamases and long in the DD-peptidases.65-67... 

Fig. 13.1. Cartoon of the aspartyl-tRNA synthetase amino acid binding site. The aspartate ligand is shown, along with the most important recognition residues. Groups that have been mutated in free energy simulations are boxed or circled. Flexible loop and Motif 2 refer to conserved motifs in the enzyme structure...

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