2q15
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | A new aspartic protease inhibitory chemotype bearing a | + | A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 microM to 11 nM K(i)) by substitution into the unoccupied S(1)' pocket. |
==About this Structure== | ==About this Structure== | ||
| Line 10: | Line 10: | ||
==Reference== | ==Reference== | ||
| - | 2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta- | + | 2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-site APP cleaving enzyme): Use of structure based design to convert a micromolar hit into a nanomolar lead., Baxter EW, Conway KA, Kennis L, Bischoff F, Mercken MH, Winter HL, Reynolds CH, Tounge BA, Luo C, Scott MK, Huang Y, Braeken M, Pieters SM, Berthelot DJ, Masure S, Bruinzeel WD, Jordan AD, Parker MH, Boyd RE, Qu J, Alexander RS, Brenneman DE, Reitz AB, J Med Chem. 2007 Sep 6;50(18):4261-4. Epub 2007 Aug 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17685503 17685503] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Sharff, A | + | [[Category: Sharff, A J.]] |
[[Category: 3MR]] | [[Category: 3MR]] | ||
[[Category: bace inhibitor complex]] | [[Category: bace inhibitor complex]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:35:04 2008'' |
Revision as of 16:35, 21 February 2008
|
Structure of BACE complexed to compound 3a
Overview
A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 microM to 11 nM K(i)) by substitution into the unoccupied S(1)' pocket.
About this Structure
2Q15 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Memapsin 2, with EC number 3.4.23.46 Full crystallographic information is available from OCA.
Reference
2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-site APP cleaving enzyme): Use of structure based design to convert a micromolar hit into a nanomolar lead., Baxter EW, Conway KA, Kennis L, Bischoff F, Mercken MH, Winter HL, Reynolds CH, Tounge BA, Luo C, Scott MK, Huang Y, Braeken M, Pieters SM, Berthelot DJ, Masure S, Bruinzeel WD, Jordan AD, Parker MH, Boyd RE, Qu J, Alexander RS, Brenneman DE, Reitz AB, J Med Chem. 2007 Sep 6;50(18):4261-4. Epub 2007 Aug 8. PMID:17685503
Page seeded by OCA on Thu Feb 21 18:35:04 2008
