Structural highlights
2a3c is a 2 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 1w9p, 1w9v, 1w9u, 2a3a, 2a3b, 2a3e |
| Activity: | Chitinase, with EC number 3.2.1.14 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Family 18 chitinases play key roles in a range of pathogenic organisms and are overexpressed in the asthmatic lung. By screening a library of marketed drug molecules, we have identified methylxanthine derivatives as possible inhibitor leads. These derivatives, theophylline, caffeine, and pentoxifylline, are used therapeutically as antiinflammatory agents, with pleiotropic mechanisms of action. Here it is shown that they are also competitive inhibitors against a fungal family 18 chitinase, with pentoxifylline being the most potent (K(i) of 37 microM). Crystallographic analysis of chitinase-inhibitor complexes revealed specific interactions with the active site, mimicking the reaction intermediate analog, allosamidin. Mutagenesis identified the key active site residues, conserved in mammalian chitinases, which contribute to inhibitor affinity. Enzyme assays also revealed that these methylxanthines are active against human chitinases.
Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes.,Rao FV, Andersen OA, Vora KA, Demartino JA, van Aalten DM Chem Biol. 2005 Sep;12(9):973-80. PMID:16183021[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rao FV, Andersen OA, Vora KA, Demartino JA, van Aalten DM. Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes. Chem Biol. 2005 Sep;12(9):973-80. PMID:16183021 doi:10.1016/j.chembiol.2005.07.009
