Structural highlights
2v00 is a 1 chain structure with sequence from Cryphonectria parasitica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | 1e5o, 1e80, 1e81, 1e82, 1eed, 1ent, 1gkt, 1gvt, 1gvu, 1gvv, 1gvw, 1gvx, 1od1, 1oew, 1oex |
| Activity: | Endothiapepsin, with EC number 3.4.23.22 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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
Fragment-based lead generation was applied to find novel small-molecule inhibitors of beta-secretase (BACE-1), a key target for the treatment of Alzheimer's disease. Fragment hits coming from a 1D NMR screen were characterized by BIAcore, and the most promising compounds were soaked into protein crystals to help the rational design of more potent hit analogues. Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overcome by using endothiapepsin as a surrogate aspartyl protease. Among others, we identified 6-substituted isocytosines as a novel warhead against BACE-1, and the accompanying paper in this journal describes how these were optimized to a lead series of nanomolar inhibitors.1.
Discovery of a novel warhead against beta-secretase through fragment-based lead generation.,Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:17985861[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH. Discovery of a novel warhead against beta-secretase through fragment-based lead generation. J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:17985861 doi:10.1021/jm070825k
