Catalytic antibody light chain capable of cleaving a chemokine receptor CCR-5 peptide with a high reaction rate constant.
A monoclonal antibody (MAb), ECL2B-2, was obtained by immunizing a peptide possessing a part of a sequence of a chemokine receptor, CCR-5, which is present as a membrane protein on the macrophage surface, and which plays an important role in human immunodeficiency virus (HIV) infection. From the DNA and the deduced amino acid sequences of the light and heavy chains of ECL2B-2 MAb, molecular modeling was conducted to calculate the steric conformation of the antibody. Modeling suggested that the structure of ECL2B-2 could possess one or two catalytic triad(s), composed of Asp(1), Ser(27a) (or Ser(27e)), and His(93) (or His(27d)), in the light chain of ECL2B-2. The three amino acid residues, Asp(1), Ser(27a), and His(93), are identical to those of catalytic antibody light chains such as VIPase and i41SL1-2. The light chain of ECL2B-2 MAb degraded the antigenic peptide CCR-5 within about 100 h. Surprisingly, the light chain had a very high catalytic reaction rate constant (k(cat)) of 2.23 min(-1), which is greater by factors of tens to hundreds than those of natural catalytic antibodies obtained previously. The heavy chain of ECL2B-2 MAb, which has no catalytic triad because of a lack of His residue, did not degrade the CCR-5 peptide.
Mitsuda
Yukie
Y
School of Biosciences, Hiroshima Prefectural University, Shobara City, Hiroshima-ken 727-0023, Japan.
Hifumi
Emi
E
Tsuruhata
Kumi
K
Fujinami
Hiroko
H
Yamamoto
Naoki
N
Uda
Taizo
T
D000595:Amino Acid Sequence; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology*; D003198:Computer Simulation; D004789:Enzyme Activation; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000276:immunology; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains; D019713:Receptors, CCR5