3HGN

Structure of porcine pancreatic elastase complexed with a potent peptidyl inhibitor FR130180 determined by neutron crystallography


Experimental Data Snapshot

  • Method: NEUTRON DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.163 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.149 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Combined High-Resolution Neutron and X-ray Analysis of Inhibited Elastase Confirms the Active-Site Oxyanion Hole but Rules against a Low-Barrier Hydrogen Bond

Tamada, T.Kinoshita, T.Kurihara, K.Adachi, M.Ohhara, T.Imai, K.Kuroki, R.Tada, T.

(2009) J Am Chem Soc 131: 11033-11040

  • DOI: https://doi.org/10.1021/ja9028846
  • Primary Citation of Related Structures:  
    3HGN, 3HGP

  • PubMed Abstract: 

    To help resolve long-standing questions regarding the catalytic activity of the serine proteases, the structure of porcine pancreatic elastase has been analyzed by high-resolution neutron and X-ray crystallography. To mimic the tetrahedral transition intermediate, a peptidic inhibitor was used. A single large crystal was used to collect room-temperature neutron data to 1.65 A resolution and X-ray data to 1.20 A resolution. Another crystal provided a low-temperature X-ray data set to 0.94 A resolution. The neutron data are to higher resolution than previously reported for a serine protease and the X-ray data are comparable with other studies. The neutron and X-ray data show that the hydrogen bond between His57 and Asp102 (chymotrypsin numbering) is 2.60 A in length and that the hydrogen-bonding hydrogen is 0.80-0.96 A from the histidine nitrogen. This is not consistent with a low-barrier hydrogen which is predicted to have the hydrogen midway between the donor and acceptor atom. The observed interaction between His57 and Asp102 is essentially a short but conventional hydrogen bond, sometimes described as a short ionic hydrogen bond. The neutron analysis also shows that the oxygen of the oxopropyl group of the inhibitor is present as an oxygen anion rather than a hydroxyl group, supporting the role of the "oxyanion hole" in stabilizing the tetrahedral intermediate in catalysis.


  • Organizational Affiliation

    Quantum Beam Science Directorate, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai, Ibaraki 319-1195, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Elastase-1240Sus 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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FRW
Query on FRW

Download Ideal Coordinates CCD File 
B [auth A]4-[[(2S)-3-methyl-1-oxo-1-[(2S)-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxo-pentan-3-yl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]carbamoyl]benzoic acid
C24 H30 F3 N3 O6
FGNPKLCZJAUKFU-BZSNNMDCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
CA
Query on CA

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

Experimental Data

  • Method: NEUTRON DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.163 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.149 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.937α = 90
b = 57.464β = 90
c = 75.18γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Data collection, Non-polymer description, Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description