Structural highlights
3wmc is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | NAG, NF6 |
| Related: | 3nsm, 3nsn, 3ozo, 3ozp, 3s6t, 3vtr, 3wmb |
| Activity: | Beta-N-acetylhexosaminidase, with EC number 3.2.1.52 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
Selective inhibition of function-specific beta-GlcNAcase has great potential in terms of drug design and biological research. The symmetrical bis-naphthalimide M-31850 was previously obtained by screening for specificity against human glycoconjugate-lytic beta-GlcNAcase. Using protein-ligand co-crystallization and molecular docking, we designed an unsymmetrical dyad of naphthalimide and thiadiazole, Q2, that changes naphthalimide specificity from against a human glycoconjugate-lytic beta-GlcNAcase to against insect and bacterial chitinolytic beta-GlcNAcases. The crystallographic and in silico studies reveal that the naphthalimide ring can be utilized to bind different parts of these enzyme homologs, providing a new starting point to design specific inhibitors. Moreover, Q2-induced closure of the substrate binding pocket is the structural basis for its 13-fold increment in inhibitory potency. Q2 is the first non-carbohydrate inhibitor against chitinolytic beta-GlcNAcases. This study provides a useful example of structure-based rationally designed inhibitors as potential pharmaceuticals or pesticides.
A crystal structure-guided rational design switching non-carbohydrate inhibitors' specificity between two beta-GlcNAcase homologs.,Liu T, Guo P, Zhou Y, Wang J, Chen L, Yang H, Qian X, Yang Q Sci Rep. 2014 Aug 26;4:6188. doi: 10.1038/srep06188. PMID:25155420[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu T, Guo P, Zhou Y, Wang J, Chen L, Yang H, Qian X, Yang Q. A crystal structure-guided rational design switching non-carbohydrate inhibitors' specificity between two beta-GlcNAcase homologs. Sci Rep. 2014 Aug 26;4:6188. doi: 10.1038/srep06188. PMID:25155420 doi:https://dx.doi.org/10.1038/srep06188
