5D1T
Anthrax toxin lethal factor with hydroxamic acid inhibitor
Summary for 5D1T
| Entry DOI | 10.2210/pdb5d1t/pdb |
| Related | 1YQY 4PKQ 4PKR 4PKS 4PKT 4PKU 4PKV 4PKW |
| Descriptor | Lethal factor, ZINC ION, N~2~-[3-(aminomethyl)benzyl]-N~2~-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide, ... (4 entities in total) |
| Functional Keywords | anthrax toxin, lethal factor, metalloproteinase, metalloprotease, structural dynamics, ligand-induced conformational change, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Bacillus anthracis |
| Total number of polymer chains | 1 |
| Total formula weight | 60896.90 |
| Authors | Maize, K.M.,Finzel, B.C. (deposition date: 2015-08-04, release date: 2015-11-11, Last modification date: 2023-09-27) |
| Primary citation | Kurbanov, E.K.,Chiu, T.L.,Solberg, J.,Francis, S.,Maize, K.M.,Fernandez, J.,Johnson, R.L.,Hawkinson, J.E.,Walters, M.A.,Finzel, B.C.,Amin, E.A. Probing the S2' Subsite of the Anthrax Toxin Lethal Factor Using Novel N-Alkylated Hydroxamates. J.Med.Chem., 58:8723-8733, 2015 Cited by PubMed Abstract: The lethal factor (LF) enzyme secreted by Bacillus anthracis is a zinc hydrolase that is chiefly responsible for anthrax-related cell death. Although many studies of the design of small molecule LF inhibitors have been conducted, no LF inhibitor is yet available as a therapeutic agent. Inhibitors with considerable chemical diversity have been developed and investigated; however, the LF S2' subsite has not yet been systematically explored as a potential target for lead optimization. Here we present synthesis, experimental evaluation, modeling, and structural biology for a novel series of sulfonamide hydroxamate LF inhibitor analogues specifically designed to extend into, and probe chemical preferences of, this S2' subsite. We discovered that this region accommodates a wide variety of chemical functionalities and that a broad selection of ligand structural modifications directed to this area can be incorporated without significant deleterious alterations in biological activity. We also identified key residues in this subsite that can potentially be targeted to improve inhibitor binding. PubMed: 26492514DOI: 10.1021/acs.jmedchem.5b01446 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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