3P4V

Human carbonic anhydrase II in complex with (+)-Xylariamide A

Summary for 3P4V

• Entry DOI: 10.2210/pdb3p4v/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, 3-chloro-N-[(2E)-4-methoxy-4-oxobut-2-enoyl]-L-tyrosine, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase, alpha type, 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: 29682.19

Authors

Hofmann, A.,Nankervis, T.,Davis, R. (deposition date: 2010-10-07, 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

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: 21332115
DOI: 10.1021/jm1013242

Experimental method

X-RAY DIFFRACTION (2 Å)