Antibodies active sites

The topologically defined region(s) on an enzyme responsible for the binding of substrate(s), coenzymes, metal ions, and protons that directly participate in the chemical transformation catalyzed by an enzyme, ribo-zyme, or catalytic antibody. Active sites need not be part of the same protein subunit, and covalently bound intermediates may interact with several regions on different subunits of a multisubunit enzyme complex. See Lambda (A) Isomers of Metal Ion-Nucleotide Complexes Lock and Key Model of Enzyme Action Low-Barrier Hydrogen Bonds Role in Catalysis Yaga-Ozav /a Plot Yonetani-Theorell Plot Induced-Fit Model Allosteric Interaction... 

Many other redox reactions are potentially amenable to antibody catalysis. For example, the chemistry of the P-450 cytochromes, including the hydroxylation of alkanes and the epoxidation of alkenes, can be mimicked with synthetic porphyrins. Incorporation of such molecules into antibody active sites could conceivably yield new catalysts that combine the intrinsic reactivity of the cofactor with the tailored selectivity of the binding pocket. Work is just beginning in this area, but preliminary studies with porphyrin haptens have yielded some interesting results.126-130 Novel redox chemistry can also be anticipated for antibodies containing metal ions, flavins, nicotinamide analogs, and other reactive moieties. 

Increased values of AH and AS for the mAh 4-4-20/monofluoresceinated peptide complexes relative to the mAh 4-4-20/fluorescein complex decay were interpreted as resulting from inclusion of the carrier peptides. Increased enthalpic contributions may have resulted from actual binding interactions between the surface accessible complementarity determining regions (CDRs) surrounding the mouth of the antibody active site and the amino acids of the peptides. Whitlow etal. (15) reported that a significant percentage of the amino acids that compose the mAb 4-4-20 CDRs were solvent accessible when fluorescein was in the active site. The increased values for AH also may have been due to differences in hydration of the antibody complexes. 

All immunoglobulin molecules have a constant carboxyl terminal end and a variable amino-terminal end. The amino-terminal end is the antibody active site or the antigen combining site, with an amino acid sequence that varies to correspond with the configuration of challenging antigens. 

The kinetic data of and -K .(per antibody active site) were obtained in PBS at pH 7.4 by fitting experimental data to nonlinear regression analysis using GRAFIT software. 

Singer, S. J., and R. F. Doohttle. 1966. Antibody active sites and immunoglobulin molecules. Science, 153 13-25. 

A catalytic antibody raised to bind the hydrophobic dye 2-bromoaceta-mido-l,5-naphthalenedisulfonate was also found to catalyze the Kemp decarboxylation, with a rate acceleration, defined as fecat/feuncat, of 10, which was roughly 1000-fold more than the acceleration brought about by the simple CTAB micelles (fecat was found to be equal to 17 min at pH 8. 0, 20 °C). It was proposed that partitioning of the substrate into the significantly hydrophobic antibody active site resulted in s pificant rate acceleration. However, subsequent structural analyses su ested a more complex active site of the antibody, with an alternation of polar and nonpolar residues. This result is in agreement with the findings in simpler systems, such as the rate acceleration brought about by the simple cationic... 

Seebeck FP, HHvert D. Positional ordering of reacting groups contributes significantly to the efficiency of proton transfer at an antibody active site.J Am Chem Soc. 2005 127 1307-1312. 

---