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2bdl

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|SITE=
|SITE=
|LIGAND= <scene name='pdbligand=4PR:(3S)-1-{[(3,5-DIMETHYLISOXAZOL-4-YL)AMINO]CARBONYL}-4,4-DIMETHYLPYRROLIDIN-3-YL{(1S)-1-[1-HYDROXY-2-OXO-2-{[(1R)-1-PHENYLETHYL]AMINO}ETHYL]PENTYL}CARBAMATE'>4PR</scene>
|LIGAND= <scene name='pdbligand=4PR:(3S)-1-{[(3,5-DIMETHYLISOXAZOL-4-YL)AMINO]CARBONYL}-4,4-DIMETHYLPYRROLIDIN-3-YL{(1S)-1-[1-HYDROXY-2-OXO-2-{[(1R)-1-PHENYLETHYL]AMINO}ETHYL]PENTYL}CARBAMATE'>4PR</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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|ACTIVITY= <span class='plainlinks'>[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] </span>
|GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|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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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bdl OCA], [http://www.ebi.ac.uk/pdbsum/2bdl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bdl RCSB]</span>
}}
}}
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==Overview==
==Overview==
Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S(3) subsite of cathepsin K. Manipulation of P3 and P1' groups afforded potent inhibitors with drug-like properties.
Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S(3) subsite of cathepsin K. Manipulation of P3 and P1' groups afforded potent inhibitors with drug-like properties.
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==Disease==
 
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Known disease associated with this structure: Pycnodysostosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601105 601105]]
 
==About this Structure==
==About this Structure==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Shewchuk, L M.]]
[[Category: Shewchuk, L M.]]
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[[Category: 4PR]]
 
[[Category: cathepsin]]
[[Category: cathepsin]]
[[Category: catk]]
[[Category: catk]]
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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 Mar 20 16:00:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:04:48 2008''

Revision as of 23:04, 30 March 2008


PDB ID 2bdl

Drag the structure with the mouse to rotate
, resolution 2.0Å
Ligands:
Gene: CTSK, CTSO, CTSO2 (Homo sapiens)
Activity: Cathepsin K, with EC number 3.4.22.38
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor


Overview

Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S(3) subsite of cathepsin K. Manipulation of P3 and P1' groups afforded potent inhibitors with drug-like properties.

About this Structure

2BDL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Novel, potent P2-P3 pyrrolidine derivatives of ketoamide-based cathepsin K inhibitors., Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Ray JA, Samano V, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1735-9. Epub 2006 Jan 11. PMID:16376075

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