Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1ym2
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1ym2.gif|left|200px]] | + | [[Image:1ym2.gif|left|200px]] |
| - | + | ||
| - | '''Crystal structure of human beta secretase complexed with NVP-AUR200''' | + | {{Structure |
| + | |PDB= 1ym2 |SIZE=350|CAPTION= <scene name='initialview01'>1ym2</scene>, resolution 2.05Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=AUA:(1R,2R)-2-{(1S,2S)-2-[(S)-2-((S)-2-ACETYLAMINO-4-METHYL-PENTANOYLAMINO)-4-METHYLSULFANYL-BUTYRYLAMINO]-1-HYDROXY-4-METHYL-PENTYL}-4-OXO-CYCLOPENTANECARBOXYLIC ACID ((S)-1-BUTYLCARBAMOYL-2-METHYL-PROPYL)-AMIDE'>AUA</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of human beta secretase complexed with NVP-AUR200''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1YM2 is a [ | + | 1YM2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YM2 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics., Hanessian S, Yun H, Hou Y, Yang G, Bayrakdarian M, Therrien E, Moitessier N, Roggo S, Veenstra S, Tintelnot-Blomley M, Rondeau JM, Ostermeier C, Strauss A, Ramage P, Paganetti P, Neumann U, Betschart C, J Med Chem. 2005 Aug 11;48(16):5175-90. PMID:[http:// | + | Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics., Hanessian S, Yun H, Hou Y, Yang G, Bayrakdarian M, Therrien E, Moitessier N, Roggo S, Veenstra S, Tintelnot-Blomley M, Rondeau JM, Ostermeier C, Strauss A, Ramage P, Paganetti P, Neumann U, Betschart C, J Med Chem. 2005 Aug 11;48(16):5175-90. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16078837 16078837] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
| Line 29: | Line 38: | ||
[[Category: memapsin2]] | [[Category: memapsin2]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:24:37 2008'' |
Revision as of 13:24, 20 March 2008
| |||||||
| , resolution 2.05Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human beta secretase complexed with NVP-AUR200
Overview
Molecular modeling based on the X-ray crystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM99-2) of BACE led to the design and synthesis of a series of constrained P(1)' analogues. A cyclopentane ring was incorporated in 1 spanning the P(1)' Ala methyl group and the adjacent methylene carbon atom of the chain. Progressive truncation at the P(2)'-P(4)' sites led to a potent truncated analogue 5 with good selectivity over Cathepsin D. Using the same backbone replacement concept, a series of cyclopentane, cyclopentanone, tetrahydrofuran, pyrrolidine, and pyrrolidinone analogues were synthesized with considerable variation at the P and P' sites. The cyclopentanone and 2-pyrrolidinone analogues 45 and 57 showed low nM BACE inhibition. X-ray cocrystal structures of two analogues 5 and 45 revealed excellent convergence with the original inhibitor 1 structure while providing new insights into other interactions which could be exploited for future modifications.
About this Structure
1YM2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics., Hanessian S, Yun H, Hou Y, Yang G, Bayrakdarian M, Therrien E, Moitessier N, Roggo S, Veenstra S, Tintelnot-Blomley M, Rondeau JM, Ostermeier C, Strauss A, Ramage P, Paganetti P, Neumann U, Betschart C, J Med Chem. 2005 Aug 11;48(16):5175-90. PMID:16078837
Page seeded by OCA on Thu Mar 20 15:24:37 2008
