Endopeptidase character of monoclonal antibody i41-7 subunits.

We prepared six anti-idiotypic monoclonal antibodies (mAbs) against parent 41S-2 mAb whose light chain is a super catalytic antibody (41S-2-L) capable of degrading targeted HIV-1gp41 molecule. Out of the obtained six mAbs, i41-7 mAb showed the strongest affinity to the parent 41S-2 mAb. The three dimensional structure of i41-7 mAb was created by molecular modeling using the deduced amino acid sequence of the light and heavy chain of i41-7 mAb. It suggests that the light and heavy chain possess catalytic triad-like structure composed of Ser, His and Asp in their conformations. Both chains of i41-7 mAb could cleave peptide bond of some peptides such as a polypeptide, TP41-1 (TPRGPDRPEGIEEEGGERDRD), as anticipated. The cleaving reaction advanced in accordance with Michaelis-Menten equation. The catalytic efficiency (kcat/Km) of light and heavy chain was 9.1 x 10(3) and 1.7 x 10(4) M(-1) x min(-1), respectively, while the intact i41-7 mAb did not exhibit any catalytic activity. The first cleaved bond of the TP41-1 peptide by the light chain was between 14E and 15G in the sequence. It was revealed that both light and heavy chains had endopeptidase characteristics.