2aux: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CT1:(1R)-2-METHYL-1-(PHENYLMETHYL)PROPYL[(1S)-1-FORMYLPENTYL]CARBAMATE'>CT1</scene> | |LIGAND= <scene name='pdbligand=CT1:(1R)-2-METHYL-1-(PHENYLMETHYL)PROPYL[(1S)-1-FORMYLPENTYL]CARBAMATE'>CT1</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] | |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]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2auz|2AUZ]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aux OCA], [http://www.ebi.ac.uk/pdbsum/2aux PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2aux RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Miller, L R.]] | [[Category: Miller, L R.]] | ||
[[Category: Shewchuk, L M.]] | [[Category: Shewchuk, L M.]] | ||
[[Category: catk]] | [[Category: catk]] | ||
[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:57:35 2008'' | ||
Revision as of 01:57, 31 March 2008
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| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CTSK, CTSO, CTSO2 (Homo sapiens) | ||||||
| Activity: | Cathepsin K, with EC number 3.4.22.38 | ||||||
| Related: | 2AUZ
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Cathepsin K complexed with a semicarbazone inhibitor
OverviewOverview
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.
About this StructureAbout this Structure
2AUX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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