2oht
From Proteopedia
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|PDB= 2oht |SIZE=350|CAPTION= <scene name='initialview01'>2oht</scene>, resolution 2.30Å | |PDB= 2oht |SIZE=350|CAPTION= <scene name='initialview01'>2oht</scene>, resolution 2.30Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=IP6:N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2,3-DIAMINE'>IP6</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= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2of0|2OF0]], [[2ohk|2OHK]], [[2ohl|2OHL]], [[2ohm|2OHM]], [[2ohn|2OHN]], [[2ohp|2OHP]], [[2ohq|2OHQ]], [[2ohr|2OHR]], [[2ohs|2OHS]], [[2ohu|2OHU]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oht OCA], [http://www.ebi.ac.uk/pdbsum/2oht PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oht RCSB]</span> | ||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Patel, S.]] | [[Category: Patel, S.]] | ||
| - | [[Category: DMS]] | ||
| - | [[Category: IOD]] | ||
| - | [[Category: IP6]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: alzheimer's disease]] | [[Category: alzheimer's disease]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''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 04:18:05 2008'' |
Revision as of 01:18, 31 March 2008
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | BACE1, BACE (Homo sapiens) | ||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Related: | 2OF0, 2OHK, 2OHL, 2OHM, 2OHN, 2OHP, 2OHQ, 2OHR, 2OHS, 2OHU
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray crystal structure of beta secretase complexed with compound 7
Overview
Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 microM) and 6c (IC50 = 24 microM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM).
About this Structure
2OHT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase., Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1124-32. Epub 2007 Feb 22. PMID:17315857
Page seeded by OCA on Mon Mar 31 04:18:05 2008
