1yt7

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[[Image:1yt7.gif|left|200px]]<br /><applet load="1yt7" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1yt7.gif|left|200px]]
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caption="1yt7, resolution 2.3&Aring;" />
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'''Cathepsin K complexed with a constrained ketoamide inhibitor'''<br />
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{{Structure
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|PDB= 1yt7 |SIZE=350|CAPTION= <scene name='initialview01'>1yt7</scene>, resolution 2.3&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=3FC:(1R)-2,2-DIMETHYL-1-({5-[4-(TRIFLUOROMETHYL)PHENYL]-1,3,4-OXADIAZOL-2-YL}METHYL)PROPYL (1S)-1-{OXO[(2-OXO-1,3-OXAZOLIDIN-3-YL)AMINO]ACETYL}PENTYLCARBAMATE'>3FC</scene>
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|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]
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|GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Cathepsin K complexed with a constrained ketoamide inhibitor'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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1YT7 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=1YT7 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15982880 15982880]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15982880 15982880]
[[Category: Cathepsin K]]
[[Category: Cathepsin K]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: cysteine protease]]
[[Category: cysteine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:08:51 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:27:09 2008''

Revision as of 13:27, 20 March 2008

Image:1yt7.gif


PDB ID 1yt7

Drag the structure with the mouse to rotate
, resolution 2.3Å
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 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. 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 Mar 20 15:27:09 2008

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