1waw: Difference between revisions
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==Overview== | ==Overview== | ||
Family 18 chitinases play key roles in organisms ranging from bacteria to, man. There is a need for specific, potent inhibitors to probe the function, of these chitinases in different organisms. Such molecules could also, provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural, product peptides, argifin and argadin, have been characterized, which, structurally mimic chitinase-chitooligosaccharide interactions and inhibit, a bacterial chitinase in the nM-mM range. Here, we show that these, inhibitors also act on human and Aspergillus fumigatus chitinases. The, structures of these enzymes in complex with argifin and argadin, together, with mutagenesis, fluorescence, and enzymology, reveal that subtle . | Family 18 chitinases play key roles in organisms ranging from bacteria to, man. There is a need for specific, potent inhibitors to probe the function, of these chitinases in different organisms. Such molecules could also, provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural, product peptides, argifin and argadin, have been characterized, which, structurally mimic chitinase-chitooligosaccharide interactions and inhibit, a bacterial chitinase in the nM-mM range. Here, we show that these, inhibitors also act on human and Aspergillus fumigatus chitinases. The, structures of these enzymes in complex with argifin and argadin, together, with mutagenesis, fluorescence, and enzymology, reveal that subtle changes, in the binding site dramatically affect affinity and selectivity. The data, show that it may be possible to develop specific chitinase inhibitors, based on the argifin/argadin scaffolds. | ||
==About this Structure== | ==About this Structure== | ||
1WAW is a | 1WAW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, RIG, GOL and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WAW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:05:30 2007'' | ||