2ohl: Difference between revisions
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|PDB= 2ohl |SIZE=350|CAPTION= <scene name='initialview01'>2ohl</scene>, resolution 2.650Å | |PDB= 2ohl |SIZE=350|CAPTION= <scene name='initialview01'>2ohl</scene>, resolution 2.650Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=2AQ:QUINOLIN-2-AMINE'>2AQ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]], [[2ohm|2OHM]], [[2ohn|2OHN]], [[2ohp|2OHP]], [[2ohq|2OHQ]], [[2ohr|2OHR]], [[2ohs|2OHS]], [[2oht|2OHT]], [[2ohu|2OHU]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ohl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ohl OCA], [http://www.ebi.ac.uk/pdbsum/2ohl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ohl RCSB]</span> | |||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Patel, S.]] | [[Category: Patel, S.]] | ||
[[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 04:17:59 2008'' | ||
Revision as of 01:18, 31 March 2008
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| 2ohl, resolution 2.650Å | |||||||||||||
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| Ligands: | 2AQ, DMS, IOD | ||||||||||||
| Gene: | BACE1, BACE (Homo sapiens) | ||||||||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||||||||
| Related: | 2OF0, 2OHK, 2OHM, 2OHN, 2OHP, 2OHQ, 2OHR, 2OHS, 2OHT, 2OHU
| ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
X-ray crystal structure of beta secretase complexed with 2-aminoquinoline
Overview
This paper describes an application of fragment screening to the aspartyl protease enzyme, beta-secretase (BACE-1), using high throughput X-ray crystallography. Three distinct chemotypes were identified by X-ray crystallography as binding to the catalytic aspartates either via an aminoheterocycle (such as 2-aminoquinoline), a piperidine, or an aliphatic hydroxyl group. The fragment hits were weak inhibitors of BACE-1 in the millimolar range but were of interest because most of them displayed relatively good ligand efficiencies. The aminoheterocycles exhibited a novel recognition motif that has not been seen before with aspartic proteases. Virtual screening around this motif identified an aminopyridine with increased potency and attractive growth points for further elaboration using structure-based drug design. The companion paper illustrates how sub-micromolar inhibitors were developed starting from this fragment.
About this Structure
2OHL 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 beta-secretase., Murray CW, Callaghan O, Chessari G, Cleasby A, Congreve M, Frederickson M, Hartshorn MJ, McMenamin R, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1116-23. Epub 2007 Feb 22. PMID:17315856
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