3CHE
Crystal structure of Aspergillus fumigatus chitinase B1 in complex with tripeptide
Summary for 3CHE
| Entry DOI | 10.2210/pdb3che/pdb |
| Related | 1W9P 1W9V 3CH9 3CHC 3CHD 3CHF |
| Descriptor | Chitinase, Peptide inhibitor, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | (beta-alpha)8 barrel, chitinase, peptide inhibitors, glycosidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Aspergillus fumigatus |
| Total number of polymer chains | 4 |
| Total formula weight | 97543.58 |
| Authors | Andersen, O.A.,van Aalten, D.M.F. (deposition date: 2008-03-09, release date: 2008-03-25, Last modification date: 2023-08-30) |
| Primary citation | Andersen, O.A.,Nathubhai, A.,Dixon, M.J.,Eggleston, I.M.,van Aalten, D.M. Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin. Chem.Biol., 15:295-301, 2008 Cited by PubMed Abstract: Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides, and antiasthmatics. Argifin, a natural product cyclopentapeptide, competitively inhibits family 18 chitinases in the nanomolar to micromolar range and shows extensive substrate mimicry. In an attempt to map the active fragments of this large natural product, the cyclopentapeptide was progressively dissected down to four linear peptides and dimethylguanylurea, synthesized using a combination of solution and solid phase peptide synthesis. The peptide fragments inhibit chitinase B1 from Aspergillus fumigatus (AfChiB1), the human chitotriosidase, and chitinase activity in lung homogenates from a murine model of chronic asthma, with potencies ranging from high nanomolar to high micromolar inhibition. X-ray crystallographic analysis of the chitinase-inhibitor complexes revealed that the conformations of the linear peptides were remarkably similar to that of the natural product. Strikingly, the dimethylguanylurea fragment, representing only a quarter of the natural product mass, was found to harbor all significant interactions with the protein and binds with unusually high efficiency. The data provide useful information that could lead to the generation of drug-like, natural product-based chitinase inhibitors. PubMed: 18355729DOI: 10.1016/j.chembiol.2008.02.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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