1tu6
From Proteopedia
(New page: 200px<br /> <applet load="1tu6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tu6, resolution 1.75Å" /> '''Cathepsin K complex...) |
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| - | [[Image:1tu6.gif|left|200px]]<br /> | + | [[Image:1tu6.gif|left|200px]]<br /><applet load="1tu6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1tu6" size=" | + | |
caption="1tu6, resolution 1.75Å" /> | caption="1tu6, resolution 1.75Å" /> | ||
'''Cathepsin K complexed with a ketoamide inhibitor'''<br /> | '''Cathepsin K complexed with a ketoamide inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A series of ketoamides were synthesized and evaluated for inhibitory | + | A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P(2) substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P(3), P(1), and P(1') moieties afforded orally bioavailable inhibitors. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TU6 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 FSP 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:// | + | 1TU6 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=FSP:'>FSP</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=1TU6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barrett, D | + | [[Category: Barrett, D G.]] |
| - | [[Category: Catalano, J | + | [[Category: Catalano, J G.]] |
| - | [[Category: Deaton, D | + | [[Category: Deaton, D N.]] |
| - | [[Category: Hassell, A | + | [[Category: Hassell, A M.]] |
| - | [[Category: Long, S | + | [[Category: Long, S T.]] |
| - | [[Category: Miller, A | + | [[Category: Miller, A B.]] |
| - | [[Category: Miller, L | + | [[Category: Miller, L R.]] |
| - | [[Category: Shewchuk, L | + | [[Category: Shewchuk, L M.]] |
| - | [[Category: Wells-Knecht, K | + | [[Category: Wells-Knecht, K J.]] |
| - | [[Category: Wright, L | + | [[Category: Wright, L L.]] |
[[Category: FSP]] | [[Category: FSP]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:22 2008'' |
Revision as of 13:17, 21 February 2008
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Cathepsin K complexed with a ketoamide inhibitor
Contents |
Overview
A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P(2) substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P(3), P(1), and P(1') moieties afforded orally bioavailable inhibitors.
Disease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this Structure
1TU6 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
Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions., Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL, Bioorg Med Chem Lett. 2004 Oct 4;14(19):4897-902. PMID:15341947
Page seeded by OCA on Thu Feb 21 15:17:22 2008
