1G9D
CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 2)
Summary for 1G9D
| Entry DOI | 10.2210/pdb1g9d/pdb |
| Related | 1epw 1f31 |
| Descriptor | BOTULINUM NEUROTOXIN TYPE B, ZINC ION, BIS(5-AMIDINO-BENZIMIDAZOLYL)METHANE, ... (4 entities in total) |
| Functional Keywords | botulinum, neurotoxin, inhibitor, complex, hydrolase |
| Biological source | Clostridium botulinum |
| Cellular location | Botulinum neurotoxin B light chain: Secreted. Botulinum neurotoxin B heavy chain: Secreted: P10844 |
| Total number of polymer chains | 1 |
| Total formula weight | 151634.96 |
| Authors | Eswaramoorthy, S.,Swaminathan, S. (deposition date: 2000-11-22, release date: 2002-11-13, Last modification date: 2024-11-13) |
| Primary citation | Eswaramoorthy, S.,Kumaran, D.,Swaminathan, S. A Novel Mechanism for Clostridium botulinum Neurotoxin Inhibition BIOCHEMISTRY, 41:9795-9802, 2002 Cited by PubMed Abstract: Clostridium botulinum neurotoxins are zinc endopeptidase proteins responsible for cleaving specific peptide bonds of proteins of neuroexocytosis apparatus. The ability of drugs to interfere with toxin's catalytic activity is being evaluated with zinc chelators and metalloprotease inhibitors. It is important to develop effective pharmacological treatment for the intact holotoxin before the catalytic domain separates and enters the cytosol. We present here evidence for a novel mechanism of an inhibitor binding to the holotoxin and for the chelation of zinc from our structural studies on Clostridium botulinum neurotoxin type B in complex with a potential metalloprotease inhibitor, bis(5-amidino-2-benzimidazolyl)methane, and provide snapshots of the reaction as it progresses. The binding and inhibition mechanism of this inhibitor to the neurotoxin seems to be unique for intact botulinum neurotoxins. The environment of the active site rearranges in the presence of the inhibitor, and the zinc ion is gradually removed from the active site and transported to a different site in the protein, probably causing loss of catalytic activity. PubMed: 12146945DOI: 10.1021/bi020060c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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