Catalytic features of monoclonal antibody i41SL1-2 subunits.
A monoclonal antibody (mAb), i41SL1-2, was obtained by immunizing the peptide of complementarity-determining region-1 (CDRL-1: RSSKSLLYSNGNTYLY) of a super catalytic antibody light chain, 41S-2-L, capable of enzymatically destroying the gp41 molecule of the HIV-1 envelope. From the DNA and the deduced amino acid sequences of the light and heavy chain of i41SL1-2 mAb, molecular modeling was conducted that suggested that both subunits of i41SL1-2 mAb possess catalytic triads in their structures. Especially the light chain of i41SL1-2 mAb possesses a characteristic catalytic triad composed of Asp(1), Ser(27A), and His(93), whose positions are identical to the catalytic antibody light chain, VIPase, of S. Paul and colleagues (see text). The antibody gene of i41SL1-2 light chain and VIPase belong to the same germline, bd2, suggesting that the discrete germline inherently possesses catalytic activity. Both light and heavy chains of i41SL1-2 mAb degraded the antigenic peptide CDRL-1 within 47 and 57 h, respectively. The catalytic reaction constant (kcat) of the light and heavy chain was 6.1 x 10(-1) and 6.2 x 10(-1) min(-1), respectively. These are high values for the natural catalytic antibodies reported so far. The catalytic efficiency (kcat/Km) of the light and heavy chain was 3.1 x 10(5) and 4.9 x 10(4) M(-1) min(-1), respectively. The first cleaved bond of the antigenic peptide by subunits of i41SL1-2 mAb was between Arg(1) and Ser(2) in the sequence of CDRL-1, suggesting a serine protease character.
Hifumi
Emi
E
Hiroshima Prefectural University, School of Biosciences, Shobara City, Hiroshima-ken 727-0023, Japan.
Kondo
Hiroyuki
H
Mitsuda
Yukie
Y
Uda
Taizo
T
D000595:Amino Acid Sequence; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology*; D002384:Catalysis; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D013237:Stereoisomerism
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; C487855:i41SL1-2 monoclonal antibody