Crystal structure of an antibody specifically recognizing 3,4-methyl enedioxy methamphetamine through the epoxide moiety.
Geonho Cheon, Dahyun Hwang, Truc Chi Le, Yeongmok Lee, Eunyoung Han, Sora An, Yeji Jung, Heesun Chung, Sangho Lee
Biochemical and biophysical research communications November 12, 2024 DOI: 10.1016/j.bbrc.2024.150607 via PubMed
Summary
AI-generated from the abstractAntibodies that detect MDMA (ecstasy) often also recognize its chemical analogue methamphetamine (METH), but two antibodies, 1bB11 and 1bF12, were identified that bind MDMA specifically without binding METH. The crystal structure of 1bB11 bound to MDMA, solved at 3.2 Å resolution, shows that key interactions involve the epoxide moiety of MDMA with residues S34 and Y36 of the antibody's light chain, and an additional interaction with E33 of the heavy chain. Mutagenesis confirmed these residues are important for binding. Comparing this structure to another antibody that binds both drugs revealed opposite binding orientations, providing a structural basis for developing a highly specific antibody for MDMA diagnosis.
Study at a glance
| Characteristics | Experimental study with structural and biochemical analysis Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | Crystal structure Epoxide moiety Meth Drug-testing drug screening |
| Citations | 2 |
| Key finding | Two antibodies, 1bB11 and 1bF12, specifically recognize MDMA and not METH, with the crystal structure of 1bB11 revealing key interactions involving the epoxide moiety and specific light and heavy chain residues. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA) or publicly known as "ecstasy" is a drug abuse substance. Since antibodies that detect MDMA typically also recognize its chemical analogue, methamphetamine (METH), we identified antibodies specifically recognizing MDMA, but not METH, named 1bB11 and 1bF12, using phage display. The crystal structure of 1bB11 in complex with MDMA was determined at 3.2 Å resolution. Key interactions were found between the epoxide moiety of MDMA and S34 and Y36 of the light chain. Additional interaction with E33 of the heavy chain contributes to anchoring MDMA. Mutagenesis-based biochemical analysis confirmed the importance of these residues in MDMA binding. Comparing the structure of 1bB11 to a scFv6H4, which binds both METH and MDMA, revealed opposite binding orientations. Taken together, our data provides a structural framework for selective binding to MDMA by the 1bB11 antibody, paving a way to develop a highly specific antibody for diagnosis.