| Structural highlights
1waw is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | , , , |
| Related: | 1guv, 1hki, 1hkj, 1hkk, 1hkm, 1lg1, 1lg2, 1lq0, 1wb0 |
| Activity: | Chitinase, with EC number 3.2.1.14 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CHIT1_HUMAN] Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.[1] [2] [3]
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 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.
Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases.,Rao FV, Houston DR, Boot RG, Aerts JM, Hodkinson M, Adams DJ, Shiomi K, Omura S, van Aalten DM Chem Biol. 2005 Jan;12(1):65-76. PMID:15664516[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Boot RG, Renkema GH, Strijland A, van Zonneveld AJ, Aerts JM. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J Biol Chem. 1995 Nov 3;270(44):26252-6. PMID:7592832
- ↑ Renkema GH, Boot RG, Muijsers AO, Donker-Koopman WE, Aerts JM. Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins. J Biol Chem. 1995 Feb 3;270(5):2198-202. PMID:7836450
- ↑ Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, de Meulemeester TM, Mannens MM, Aerts JM. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem. 1998 Oct 2;273(40):25680-5. PMID:9748235
- ↑ Rao FV, Houston DR, Boot RG, Aerts JM, Hodkinson M, Adams DJ, Shiomi K, Omura S, van Aalten DM. Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases. Chem Biol. 2005 Jan;12(1):65-76. PMID:15664516 doi:http://dx.doi.org/10.1016/j.chembiol.2004.10.013
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