Structural highlights
1w1t is a 2 chain structure with sequence from "bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , |
| Related: | 1e15, 1e6n, 1e6p, 1e6r, 1e6z, 1goi, 1gpf, 1ogb, 1ur8, 1ur9, 1w1p, 1w1v, 1w1y |
| Activity: | Chitinase, with EC number 3.2.1.14 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhibits family 18 chitinases by mimicking the structure of the proposed reaction intermediate. Here we report the high-resolution structures of four new CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro), and cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition, details of enzyme inhibition and in vivo activity against Saccharomyces cerevisiae are presented. The structures reveal that the common cyclo-(Gly-Pro) substructure is sufficient for binding, allowing modification of the side chain of the nonproline residue. This suggests that design of cyclic dipeptides with a view to increasing inhibition of family 18 chitinases should be possible through relatively accessible chemistry. The derivatives presented here in complex with chitinase B from Serratia marcescens provide further insight into the mechanism of inhibition of chitinases by cyclic dipeptides as well as providing a new scaffold for chitinase inhibitor design.
Structure-based exploration of cyclic dipeptide chitinase inhibitors.,Houston DR, Synstad B, Eijsink VG, Stark MJ, Eggleston IM, van Aalten DM J Med Chem. 2004 Nov 4;47(23):5713-20. PMID:15509170[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Houston DR, Synstad B, Eijsink VG, Stark MJ, Eggleston IM, van Aalten DM. Structure-based exploration of cyclic dipeptide chitinase inhibitors. J Med Chem. 2004 Nov 4;47(23):5713-20. PMID:15509170 doi:10.1021/jm049940a
