7KYF
Botulism Neurooxin Light Chain A app form
Summary for 7KYF
| Entry DOI | 10.2210/pdb7kyf/pdb |
| Descriptor | Bont/A1, ZINC ION, N-[(3,5-dichlorophenyl)sulfonyl]-L-isoleucyl-N-hydroxy-L-norvalinamide, ... (4 entities in total) |
| Functional Keywords | bont, botulinum neurotoxin nva-ila dipetpide bound, toxin |
| Biological source | Clostridium botulinum |
| Total number of polymer chains | 1 |
| Total formula weight | 48296.82 |
| Authors | Ortega, M.E.,Salzameda, N.T. (deposition date: 2020-12-07, release date: 2021-04-14, Last modification date: 2023-10-18) |
| Primary citation | Amezcua, M.,Cruz, R.S.,Ku, A.,Moran, W.,Ortega, M.E.,Salzameda, N.T. Discovery of Dipeptides as Potent Botulinum Neurotoxin A Light-Chain Inhibitors. Acs Med.Chem.Lett., 12:295-301, 2021 Cited by PubMed Abstract: The botulinum neurotoxin, the caustic agent that causes botulism, is the most lethal toxin known to man. The neurotoxin composed of a heavy chain (HC) and a light chain (LC) enters neurons and cleaves SNARE proteins, leading to flaccid paralysis, which, in severe occurrences, can result in death. A therapeutic target for botulinum neurotoxin (BoNT) intoxication is the LC, a zinc metalloprotease that directly cleaves SNARE proteins. Herein we report dipeptides containing an aromatic connected to the N-terminus via a sulfonamide and a hydroxamic acid at the C-terminus as BoNT/A LC inhibitors. On the basis of a structure-activity relationship study, was discovered to inhibit the BoNT/A LC with an IC of 21 nM. X-ray crystallography analysis of and revealed that the dipeptides inhibit through a competitive mechanism and identified several key intermolecular interactions. PubMed: 33603978DOI: 10.1021/acsmedchemlett.0c00674 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.33 Å) |
Structure validation
Download full validation report
