1B0E

CRYSTAL STRUCTURE OF PORCINE PANCREATIC ELASTASE WITH MDL 101,146


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.180 
  • R-Value Observed: 0.180 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

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, 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.

(1998) J Med Chem 41: 2461-2480

  • DOI: https://doi.org/10.1021/jm970812e
  • Primary Citation of Related Structures:  
    1B0E, 1B0F

  • 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.


  • Organizational Affiliation

    Hoechst Marion Roussel Inc., 2110 East Galbraith Road, Cincinnati, Ohio 45215, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (ELASTASE)240Sus scrofaMutation(s): 0 
EC: 3.4.21.36
UniProt
Find proteins for P00772 (Sus scrofa)
Explore P00772 
Go to UniProtKB:  P00772
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00772
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SEI
Query on SEI

Download Ideal Coordinates CCD File 
C [auth A]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
C29 H37 F5 N4 O6
XQAMVCHQGHAELT-FKBYEOEOSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
B [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.180 
  • R-Value Observed: 0.180 
  • Space Group: P 31
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.1α = 90
b = 69.1β = 90
c = 51.1γ = 120
Software Package:
Software NamePurpose
XDSdata scaling
XSCALEdata scaling
X-PLORmodel building
X-PLORrefinement
XDSdata reduction
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-11-18
    Type: Initial release
  • Version 1.1: 2008-04-26
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description