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1ym4
From Proteopedia
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|PDB= 1ym4 |SIZE=350|CAPTION= <scene name='initialview01'>1ym4</scene>, resolution 2.25Å | |PDB= 1ym4 |SIZE=350|CAPTION= <scene name='initialview01'>1ym4</scene>, resolution 2.25Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=AMK:(S)-4-AMINO-4-{(S)-1-[(S)-2-CARBAMOYL-1-((S)-1-{(S)-[(1R,2R)-2-((S)-1-CARBOXY-ETHYLCARBAMOYL)-CYCLOPENTYL]-HYDROXY-METHYL}-3-METHYL-BUTYLCARBAMOYL)-ETHYLCARBAMOYL]-2-METHYL-PROPYLCARBAMOYL}-BUTYRIC ACID'>AMK</scene> | + | |LIGAND= <scene name='pdbligand=AMK:(S)-4-AMINO-4-{(S)-1-[(S)-2-CARBAMOYL-1-((S)-1-{(S)-[(1R,2R)-2-((S)-1-CARBOXY-ETHYLCARBAMOYL)-CYCLOPENTYL]-HYDROXY-METHYL}-3-METHYL-BUTYLCARBAMOYL)-ETHYLCARBAMOYL]-2-METHYL-PROPYLCARBAMOYL}-BUTYRIC+ACID'>AMK</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1ym2|1YM2]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ym4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ym4 OCA], [http://www.ebi.ac.uk/pdbsum/1ym4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ym4 RCSB]</span> | ||
}} | }} | ||
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[[Category: Yang, G.]] | [[Category: Yang, G.]] | ||
[[Category: Yun, H.]] | [[Category: Yun, H.]] | ||
| - | [[Category: AMK]] | ||
[[Category: alzheimer's disease]] | [[Category: alzheimer's disease]] | ||
[[Category: aspartic protease]] | [[Category: aspartic protease]] | ||
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[[Category: memapsin2]] | [[Category: memapsin2]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:12:52 2008'' |
Revision as of 22:13, 30 March 2008
| |||||||
| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Related: | 1YM2
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human beta secretase complexed with NVP-AMK640
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
1YM4 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
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