2aux
From Proteopedia
(New page: 200px<br /> <applet load="2aux" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aux, resolution 2.4Å" /> '''Cathepsin K complexe...) |
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| - | [[Image:2aux.gif|left|200px]]<br /> | + | [[Image:2aux.gif|left|200px]]<br /><applet load="2aux" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2aux" size=" | + | |
caption="2aux, resolution 2.4Å" /> | caption="2aux, resolution 2.4Å" /> | ||
'''Cathepsin K complexed with a semicarbazone inhibitor'''<br /> | '''Cathepsin K complexed with a semicarbazone inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of | + | Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AUX 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 CT1 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 2AUX 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=CT1:'>CT1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=2AUX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Adkison, K | + | [[Category: Adkison, K K.]] |
| - | [[Category: Barrett, D | + | [[Category: Barrett, D G.]] |
| - | [[Category: Deaton, D | + | [[Category: Deaton, D N.]] |
| - | [[Category: Gampe, R | + | [[Category: Gampe, R T.]] |
| - | [[Category: Hassell, A | + | [[Category: Hassell, A M.]] |
| - | [[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: Shewchuk, L | + | [[Category: Shewchuk, L M.]] |
[[Category: CT1]] | [[Category: CT1]] | ||
[[Category: catk]] | [[Category: catk]] | ||
[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:31:20 2008'' |
Revision as of 14:31, 21 February 2008
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Cathepsin K complexed with a semicarbazone inhibitor
Contents |
Overview
Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.
Disease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this Structure
2AUX is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Cathepsin K, with EC number 3.4.22.38 Full crystallographic information is available from OCA.
Reference
Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?, Adkison KK, Barrett DG, Deaton DN, Gampe RT, Hassell AM, Long ST, McFadyen RB, Miller AB, Miller LR, Payne JA, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL, Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83. Epub 2005 Nov 15. PMID:16290936
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