Practice question

Abzymes catalytic antibodies merge Ig antigen-binding specificity enzyme-like rate acceleration accelerating chemical transformations difficult natural enzymes. Generation exploits transition state analog theory Pauling: enzyme binds transition state tighter substrate lowering activation energy. Immunization stable mimic tetrahedral high-energy intermediate ester hydrolysis phosphonate ester phosphorus replacing carbon maintaining tetrahedral but stable replaces labile carbonyl elicits immune response producing antibodies binding pocket complementary transition state geometry providing binding energy offsetting barrier. Resulting Igs contain catalytic residues histidine general base abstracting proton water generating hydroxide nucleophile serine acyl enzyme intermediate tyrosine bound zinc cofactor Lewis acid polarizing carbonyl facilitating nucleophilic attack similar carboxypeptidase. Rate enhancements 10^2 to 10^5 over background Michaelis constant micromolar catalytic turnover minute lower natural enzymes 10 per minute versus 10000 but sufficient prodrug activation where high local antibody concentration compensates. Engineering mutagenesis CDRs introducing histidine improving positioning catalytic groups enhances efficiency proximity effect. Applications envision site-specific activation chemotherapy beta-lactam hydrolysis cocaine hydrolysis amyloid beta peptide cleavage Alzheimer inspired specificities absent natural proteome.