1B0F

CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146

Summary for 1B0F

• Entry DOI: 10.2210/pdb1b0f/pdb
• Descriptor: PROTEIN (ELASTASE), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 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, ... (4 entities in total)
• Functional Keywords: serine protease, fluoroethyl ketones, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 25007.55

Authors

Schreuder, H.A.,Metz, W.A.,Peet, N.P.,Pelton, J.T.,Tardif, C. (deposition date: 1998-11-09, release date: 1998-11-09, Last modification date: 2024-11-20)

Primary citation

Cregge, R.J.,Durham, S.L.,Farr, R.A.,Gallion, S.L.,Hare, C.M.,Hoffman, R.V.,Janusz, M.J.,Kim, H.O.,Koehl, J.R.,Mehdi, S.,Metz, W.A.,Peet, N.P.,Pelton, J.T.,Schreuder, H.A.,Sunder, S.,Tardif, C.
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.
J.Med.Chem., 41:2461-2480, 1998

PubMed Abstract: 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.

PubMed: 9651152
DOI: 10.1021/jm970812e

Experimental method

X-RAY DIFFRACTION (3 Å)