1b0f

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[[Image:1b0f.gif|left|200px]]<br /><applet load="1b0f" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1b0f.gif|left|200px]]
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caption="1b0f, resolution 3.00&Aring;" />
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'''CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146'''<br />
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{{Structure
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|PDB= 1b0f |SIZE=350|CAPTION= <scene name='initialview01'>1b0f</scene>, resolution 3.00&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SEI:1-{3-METHYL-2-[4-(MORPHOLINE-4-CARBONYL)-BENZOYLAMINO]-BUTYRYL}-PYRROLIDINE-2-CARBOXYLIC ACID (3,3,4,4,4-PENTAFLUORO-1-ISOPROPYL-2-OXO-BUTYL)-AMIDE'>SEI</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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1B0F 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=1B0F OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9651152 9651152]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/9651152 9651152]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Leukocyte elastase]]
[[Category: Leukocyte elastase]]
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[[Category: Tardif, C.]]
[[Category: Tardif, C.]]
[[Category: SEI]]
[[Category: SEI]]
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[[Category: fluoroethyl ketones]]
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[[Category: fluoroethyl ketone]]
[[Category: serine protease]]
[[Category: serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:50:14 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:04:39 2008''

Revision as of 08:04, 20 March 2008

Image:1b0f.gif


PDB ID 1b0f

Drag the structure with the mouse to rotate
, resolution 3.00Å
Ligands:
Activity: Leukocyte elastase, with EC number 3.4.21.37
Coordinates: save as pdb, mmCIF, xml



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. 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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