1WB0

specificity and affinity of natural product cyclopentapeptide inhibitor Argifin against human chitinase

Summary for 1WB0

• Entry DOI: 10.2210/pdb1wb0/pdb
• Related: 1GUV 1HKI 1HKJ 1HKK 1HKM 1LG1 1LG2 1LQ0 1WAW
• Related PRD ID: PRD_000465
• Descriptor: CHITOTRIOSIDASE 1, ARGIFIN, ISOPROPYL ALCOHOL, ... (6 entities in total)
• Functional Keywords: cyclopentapeptide inhibitors, chitinase inhibitors, carbohydrate metabolism, chitin degradation, chitin-binding, glycosidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: Q13231
• Total number of polymer chains: 2
• Total formula weight: 50654.39

Authors

Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Hodkinson, M.,Adams, D.J.,Shiomi, K.,Omura, S.,Van Aalten, D.M.F. (deposition date: 2004-10-29, release date: 2005-01-28, Last modification date: 2023-12-13)

Primary citation

Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Hodkinson, M.,Adams, D.J.,Shiomi, K.,Omura, S.,Van Aalten, D.M.F.
Specificity and Affinity of Natural Product Cyclopentapeptide Inhibitors Against Aspergillus Fumigatus, Human and Bacterial Chitinases
Chem.Biol., 12:65-, 2005

PubMed Abstract: 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.

PubMed: 15664516
DOI: 10.1016/J.CHEMBIOL.2004.10.013

Experimental method

X-RAY DIFFRACTION (1.65 Å)