2fs4
From Proteopedia
(New page: 200px<br /> <applet load="2fs4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fs4, resolution 2.2Å" /> '''Ketopiperazine-Based...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2fs4.gif|left|200px]]<br /> | + | [[Image:2fs4.gif|left|200px]]<br /><applet load="2fs4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fs4" size=" | + | |
caption="2fs4, resolution 2.2Å" /> | caption="2fs4, resolution 2.2Å" /> | ||
'''Ketopiperazine-Based Renin Inhibitors: Optimization of the C ring'''<br /> | '''Ketopiperazine-Based Renin Inhibitors: Optimization of the C ring'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A systematic investigation of the S3 sub-pocket activity requirements was | + | A systematic investigation of the S3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S3 sub-pocket for optimal renin inhibition. Polar groups in the S3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with clog P's < or = 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2FS4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PZ1 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Renin Renin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] Full crystallographic information is available from [http:// | + | 2FS4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PZ1:'>PZ1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Renin Renin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FS4 OCA]. |
==Reference== | ==Reference== | ||
| Line 21: | Line 20: | ||
[[Category: C.]] | [[Category: C.]] | ||
[[Category: Caia, C.]] | [[Category: Caia, C.]] | ||
| - | [[Category: Chenga, X | + | [[Category: Chenga, X M.]] |
| - | [[Category: Codya, W | + | [[Category: Codya, W L.]] |
| - | [[Category: Downinga, D | + | [[Category: Downinga, D M.]] |
| - | [[Category: Edmundsa, J | + | [[Category: Edmundsa, J J.]] |
[[Category: Erasgaa, N.]] | [[Category: Erasgaa, N.]] | ||
[[Category: Hallc, E.]] | [[Category: Hallc, E.]] | ||
| - | [[Category: Holsworth, D | + | [[Category: Holsworth, D D.]] |
[[Category: Jalaiea, M.]] | [[Category: Jalaiea, M.]] | ||
[[Category: Kasanic, A.]] | [[Category: Kasanic, A.]] | ||
| Line 34: | Line 33: | ||
[[Category: Maitic, S.]] | [[Category: Maitic, S.]] | ||
[[Category: McConnella, P.]] | [[Category: McConnella, P.]] | ||
| - | [[Category: Powella, N | + | [[Category: Powella, N A.]] |
[[Category: Rahimc, M.]] | [[Category: Rahimc, M.]] | ||
| - | [[Category: Ryanb, M | + | [[Category: Ryanb, M J.]] |
[[Category: Stiera, M.]] | [[Category: Stiera, M.]] | ||
[[Category: Subedic, R.]] | [[Category: Subedic, R.]] | ||
| Line 43: | Line 42: | ||
[[Category: protein-ligand complexes]] | [[Category: protein-ligand complexes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:33 2008'' |
Revision as of 15:24, 21 February 2008
|
Ketopiperazine-Based Renin Inhibitors: Optimization of the C ring
Contents |
Overview
A systematic investigation of the S3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S3 sub-pocket for optimal renin inhibition. Polar groups in the S3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with clog P's < or = 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity.
Disease
Known diseases associated with this structure: Hyperproreninemia OMIM:[179820], Renal tubular dysgenesis OMIM:[179820]
About this Structure
2FS4 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Renin, with EC number 3.4.23.15 Full crystallographic information is available from OCA.
Reference
Ketopiperazine-based renin inhibitors: optimization of the "C" ring., Holsworth DD, Cai C, Cheng XM, Cody WL, Downing DM, Erasga N, Lee C, Powell NA, Edmunds JJ, Stier M, Jalaie M, Zhang E, McConnell P, Ryan MJ, Bryant J, Li T, Kasani A, Hall E, Subedi R, Rahim M, Maiti S, Bioorg Med Chem Lett. 2006 May 1;16(9):2500-4. Epub 2006 Feb 15. PMID:16480874
Page seeded by OCA on Thu Feb 21 17:24:33 2008
Categories: Homo sapiens | Renin | Single protein | Bryantb, J. | C. | Caia, C. | Chenga, X M. | Codya, W L. | Downinga, D M. | Edmundsa, J J. | Erasgaa, N. | Hallc, E. | Holsworth, D D. | Jalaiea, M. | Kasanic, A. | Leea, | Lic, T. | Maitic, S. | McConnella, P. | Powella, N A. | Rahimc, M. | Ryanb, M J. | Stiera, M. | Subedic, R. | Zhanga, E. | PZ1 | Protein-ligand complexes
