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Crystal structure of an antibody specifically recognizing lorazepam suggests a common structural motif for general recognition of benzodiazepines
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DOI：10.1002/bkcs.70126.png)
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Abstract
En 中文
Lorazepam is a benzodiazepine psychoactive drug used to relieve anxiety and tension; however, it carries potential risks of dependence and abuse. In this study, we isolated two antibodies, L1A3 and L1B1, that specifically recognize lorazepam from synthetic human scFv libraries using phage display. We determined the crystal structure of L1B1 in its Fab format at a resolution of 2.3 & Aring; by introducing two sets of mutations: one in the elbow linker region and the other in a loop region. Molecular docking of lorazepam with L1B1 suggested that two chlorobenzene moieties face predominantly hydrophobic pockets of L1B1. Predicted binding interface residues of L1B1 were functionally validated by biochemical analyses combined with mutagenesis. Docking of other benzodiazepines to the crystal structure of L1B1 implicated that benzene derivative moieties would face the same pocket of L1B1, providing insights into the broad neutralizing ability of L1B1. Taken together, these results establish the structural basis of the recognition of lorazepam and benzodiazepines by L1B1, offering valuable insights for developing highly specific antibodies for diagnostic or therapeutic applications.
Keywords:
antibody
benzodiazepine
lorazepam
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2.2
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