1yt7
From Proteopedia
(New page: 200px<br /> <applet load="1yt7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yt7, resolution 2.3Å" /> '''Cathepsin K complexe...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1yt7.gif|left|200px]]<br /> | + | [[Image:1yt7.gif|left|200px]]<br /><applet load="1yt7" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yt7" size=" | + | |
caption="1yt7, resolution 2.3Å" /> | caption="1yt7, resolution 2.3Å" /> | ||
'''Cathepsin K complexed with a constrained ketoamide inhibitor'''<br /> | '''Cathepsin K complexed with a constrained ketoamide inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | An orally bioavailable series of ketoamide-based cathepsin K inhibitors | + | An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1YT7 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 SO4 and 3FC as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] Full crystallographic information is available from [http:// | + | 1YT7 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=SO4:'>SO4</scene> and <scene name='pdbligand=3FC:'>3FC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YT7 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barrett, D | + | [[Category: Barrett, D G.]] |
| - | [[Category: Boncek, V | + | [[Category: Boncek, V M.]] |
| - | [[Category: Catalano, J | + | [[Category: Catalano, J G.]] |
| - | [[Category: Deaton, D | + | [[Category: Deaton, D N.]] |
| - | [[Category: Hassell, A | + | [[Category: Hassell, A M.]] |
| - | [[Category: Jurgensen, C | + | [[Category: Jurgensen, C H.]] |
| - | [[Category: Long, S | + | [[Category: Long, S T.]] |
| - | [[Category: McFadyen, R | + | [[Category: McFadyen, R B.]] |
| - | [[Category: Miller, A | + | [[Category: Miller, A B.]] |
| - | [[Category: Miller, L | + | [[Category: Miller, L R.]] |
| - | [[Category: Payne, J | + | [[Category: Payne, J A.]] |
| - | [[Category: Ray, J | + | [[Category: Ray, J A.]] |
[[Category: Samano, V.]] | [[Category: Samano, V.]] | ||
| - | [[Category: Shewchuk, L | + | [[Category: Shewchuk, L M.]] |
| - | [[Category: Tavares, F | + | [[Category: Tavares, F X.]] |
| - | [[Category: Wells-Knecht, K | + | [[Category: Wells-Knecht, K J.]] |
| - | [[Category: Willard, D | + | [[Category: Willard, D H.]] |
| - | [[Category: Wright, L | + | [[Category: Wright, L L.]] |
| - | [[Category: Zhou, H | + | [[Category: Zhou, H Q.]] |
[[Category: 3FC]] | [[Category: 3FC]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
| Line 42: | Line 41: | ||
[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:08:51 2008'' |
Revision as of 14:08, 21 February 2008
|
Cathepsin K complexed with a constrained ketoamide inhibitor
Contents |
Overview
An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.
Disease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this Structure
1YT7 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Cathepsin K, with EC number 3.4.22.38 Full crystallographic information is available from OCA.
Reference
P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K., Barrett DG, Boncek VM, Catalano JG, Deaton DN, Hassell AM, Jurgensen CH, Long ST, McFadyen RB, Miller AB, Miller LR, Payne JA, Ray JA, Samano V, Shewchuk LM, Tavares FX, Wells-Knecht KJ, Willard DH Jr, Wright LL, Zhou HQ, Bioorg Med Chem Lett. 2005 Aug 1;15(15):3540-6. PMID:15982880
Page seeded by OCA on Thu Feb 21 16:08:51 2008
Categories: Cathepsin K | Homo sapiens | Single protein | Barrett, D G. | Boncek, V M. | Catalano, J G. | Deaton, D N. | Hassell, A M. | Jurgensen, C H. | Long, S T. | McFadyen, R B. | Miller, A B. | Miller, L R. | Payne, J A. | Ray, J A. | Samano, V. | Shewchuk, L M. | Tavares, F X. | Wells-Knecht, K J. | Willard, D H. | Wright, L L. | Zhou, H Q. | 3FC | SO4 | Cathepsin | Cysteine protease
