2FX6

bovine trypsin complexed with 2-aminobenzamidazole

  • Classification: HYDROLASE
  • Organism(s): Bos taurus
  • Mutation(s): No 

  • Deposited: 2006-02-03 Released: 2006-02-14 
  • Deposition Author(s): Katz, B.A.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure-guided design of Peptide-based tryptase inhibitors.

McGrath, M.E.Sprengeler, P.A.Hirschbein, B.Somoza, J.R.Lehoux, I.Janc, J.W.Gjerstad, E.Graupe, M.Estiarte, A.Venkataramani, C.Liu, Y.Yee, R.Ho, J.D.Green, M.J.Lee, C.-S.Liu, L.Tai, V.Spencer, J.Sperandio, D.Katz, B.A.

(2006) Biochemistry 45: 5964-5973

  • DOI: https://doi.org/10.1021/bi060173m
  • Primary Citation of Related Structures:  
    2FPZ, 2FS8, 2FS9, 2FWW, 2FX4, 2FX6, 2FXR

  • PubMed Abstract: 

    Improved peptide-based inhibitors of human beta tryptase were discovered using information gleaned from tripeptide library screening and structure-guided design methods, including fragment screening. Our efforts sought to improve this class of inhibitors by replacing the traditional Lys or Arg P1 element. The optimized compounds display low nanomolar potency against the mast cell target and several hundred-fold selectivity with respect to serine protease off targets. Thus, replacement of Lys/Arg at P1 in a peptide-like scaffold does not need to be accompanied by a loss in target affinity.


  • Organizational Affiliation

    Celera Genomics, Inc., 180 Kimball Way, South San Francisco, California 94080, USA. mary.mcgrath@gilead.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Trypsin223Bos taurusMutation(s): 0 
EC: 3.4.21.4
UniProt
Find proteins for P00760 (Bos taurus)
Explore P00760 
Go to UniProtKB:  P00760
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00760
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
270 PDBBind:  2FX6 Ki: 2.00e+5 (nM) from 1 assay(s)
Binding MOAD:  2FX6 Ki: 2.00e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.71α = 90
b = 63.2β = 90
c = 69.5γ = 90
Software Package:
Software NamePurpose
CrystalCleardata reduction
X-PLORrefinement
CrystalCleardata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2006-02-14 
  • Deposition Author(s): Katz, B.A.

Revision History  (Full details and data files)

  • Version 1.0: 2006-02-14
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description