3NB5
Human carbonic anhydrase II in complex with 2-(3-chloro-4-hydroxyphenyl)-N-(4-sulfamoylphenethyl)acetamide
Summary for 3NB5
| Entry DOI | 10.2210/pdb3nb5/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 2-(3-chloro-4-hydroxyphenyl)-N-[2-(4-sulfamoylphenyl)ethyl]acetamide, ... (5 entities in total) |
| Functional Keywords | drug design, natural product, sulfamate, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P00918 |
| Total number of polymer chains | 1 |
| Total formula weight | 29999.59 |
| Authors | Hofmann, A.,Osman, A.,Davis, R.A. (deposition date: 2010-06-02, release date: 2011-04-20, Last modification date: 2023-11-01) |
| Primary citation | Davis, R.A.,Hofmann, A.,Osman, A.,Hall, R.A.,Muhlschlegel, F.A.,Vullo, D.,Innocenti, A.,Supuran, C.T.,Poulsen, S.A. Natural Product-Based Phenols as Novel Probes for Mycobacterial and Fungal Carbonic Anhydrases J.Med.Chem., 54:1682-1692, 2011 Cited by PubMed Abstract: In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as α-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal β-CAs, with the two best performing compounds displaying submicromolar inhibition with a preference for fungal over human CA inhibition of more than 2 orders of magnitude. These compounds provide the first example of non-sulfonamide inhibitors that display β over α CA enzyme selectivity. Structural characterization of the library compounds in complex with human CA II revealed a novel binding mode whereby a methyl ester interacts via a water molecule with the active site zinc. PubMed: 21332115DOI: 10.1021/jm1013242 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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