2a3c
From Proteopedia
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Crystal structure of Aspergillus fumigatus chitinase B1 in complex with pentoxifylline
Overview
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.
About this Structure
2A3C is a Single protein structure of sequence from Aspergillus fumigatus with and as ligands. Active as Chitinase, with EC number 3.2.1.14 Full crystallographic information is available from OCA.
Reference
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
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