7Z5U
Crystal structure of the peptidase domain of collagenase G from Clostridium histolyticum in complex with a hydroxamate-based inhibitor
Summary for 7Z5U
| Entry DOI | 10.2210/pdb7z5u/pdb |
| Related | 2y6i |
| Descriptor | Collagenase ColG, ZINC ION, (2~{R})-~{N}-[2-[4-[(2-acetamidophenoxy)methyl]-1,2,3-triazol-1-yl]ethyl]-2-(2-methylpropyl)-~{N}'-oxidanyl-propanediamide, ... (5 entities in total) |
| Functional Keywords | collagenase, hydroxamate, colg, inhibitor, complex, hydrolase |
| Biological source | Hathewaya histolytica |
| Total number of polymer chains | 1 |
| Total formula weight | 48423.84 |
| Authors | Schoenauer, E.,Brandstetter, H. (deposition date: 2022-03-10, release date: 2022-11-09, Last modification date: 2024-01-31) |
| Primary citation | Alhayek, A.,Abdelsamie, A.S.,Schonauer, E.,Camberlein, V.,Hutterer, E.,Posselt, G.,Serwanja, J.,Blochl, C.,Huber, C.G.,Haupenthal, J.,Brandstetter, H.,Wessler, S.,Hirsch, A.K.H. Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases. J.Med.Chem., 65:12933-12955, 2022 Cited by PubMed Abstract: In view of the worldwide antimicrobial resistance (AMR) threat, new bacterial targets and anti-infective agents are needed. Since important roles in bacterial pathogenesis have been demonstrated for the collagenase H and G (ColH and ColG) from , collagenase Q1 and A (ColQ1 and ColA) from represent attractive antivirulence targets. Furthermore, repurposing FDA-approved drugs may assist to tackle the AMR crisis and was addressed in this work. Here, we report on the discovery of two potent and chemically stable bacterial collagenase inhibitors: synthesized and FDA-approved diphosphonates and hydroxamates. Both classes showed high activity against the clostridial and bacillary collagenases. The potent diphosphonates reduced -mediated detachment and death of cells and larvae. The hydroxamates were also tested in a similar manner; they did not have an effect in infection models. This might be due to their fast binding kinetics to bacterial collagenases. PubMed: 36154055DOI: 10.1021/acs.jmedchem.2c00785 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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