1b0f
From Proteopedia
(New page: 200px<br /> <applet load="1b0f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b0f, resolution 3.00Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1b0f.gif|left|200px]]<br /> | + | [[Image:1b0f.gif|left|200px]]<br /><applet load="1b0f" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1b0f" size=" | + | |
caption="1b0f, resolution 3.00Å" /> | caption="1b0f, resolution 3.00Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A series of P2-modified, orally active peptidic inhibitors of human | + | A series of P2-modified, orally active peptidic inhibitors of human neutrophil elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were designed using pentafluoroethyl ketone 1 as a model. Rational structural modifications were made at the P3, P2, and activating group (AG) portions of 1 based on structure-activity relationships (SAR) developed from in vitro (measured Ki) data and information provided by modeling studies that docked inhibitor 1 into the active site of HNE. The modeling-based design was corroborated with X-ray crystallographic analysis of the complex between 1 and porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1B0F 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 SEI as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] Full crystallographic information is available from [http:// | + | 1B0F 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=SEI:'>SEI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0F OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Leukocyte elastase]] | [[Category: Leukocyte elastase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Metz, W | + | [[Category: Metz, W A.]] |
| - | [[Category: Peet, N | + | [[Category: Peet, N P.]] |
| - | [[Category: Pelton, J | + | [[Category: Pelton, J T.]] |
| - | [[Category: Schreuder, H | + | [[Category: Schreuder, H A.]] |
[[Category: Tardif, C.]] | [[Category: Tardif, C.]] | ||
[[Category: SEI]] | [[Category: SEI]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:50:14 2008'' |
Revision as of 09:50, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146
Contents |
Overview
A series of P2-modified, orally active peptidic inhibitors of human neutrophil elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were designed using pentafluoroethyl ketone 1 as a model. Rational structural modifications were made at the P3, P2, and activating group (AG) portions of 1 based on structure-activity relationships (SAR) developed from in vitro (measured Ki) data and information provided by modeling studies that docked inhibitor 1 into the active site of HNE. The modeling-based design was corroborated with X-ray crystallographic analysis of the complex between 1 and porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE.
Disease
Known diseases associated with this structure: Hematopoiesis, cyclic OMIM:[130130], Neutropenia, congenital OMIM:[130130]
About this Structure
1B0F is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Leukocyte elastase, with EC number 3.4.21.37 Full crystallographic information is available from OCA.
Reference
Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally active peptidyl pentafluoroethyl ketones., Cregge RJ, Durham SL, Farr RA, Gallion SL, Hare CM, Hoffman RV, Janusz MJ, Kim HO, Koehl JR, Mehdi S, Metz WA, Peet NP, Pelton JT, Schreuder HA, Sunder S, Tardif C, J Med Chem. 1998 Jul 2;41(14):2461-80. PMID:9651152
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