1tu6
From Proteopedia
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| - | [[Image:1tu6.gif|left|200px]] | + | [[Image:1tu6.gif|left|200px]] |
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| - | '''Cathepsin K complexed with a ketoamide inhibitor''' | + | {{Structure |
| + | |PDB= 1tu6 |SIZE=350|CAPTION= <scene name='initialview01'>1tu6</scene>, resolution 1.75Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=FSP:[1-(4-FLUOROBENZYL)CYCLOBUTYL]METHYL (1S)-1-[OXO(1H-PYRAZOL-5-YLAMINO)ACETYL]PENTYLCARBAMATE'>FSP</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Cathepsin K complexed with a ketoamide inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TU6 is a [ | + | 1TU6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TU6 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15341947 15341947] |
[[Category: Cathepsin K]] | [[Category: Cathepsin K]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:23:14 2008'' |
Revision as of 12:23, 20 March 2008
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| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | CTSK, CTSO, CTSO2 (Homo sapiens) | ||||||
| Activity: | Cathepsin K, with EC number 3.4.22.38 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Mar 20 14:23:14 2008
