5ZFH

Mouse Kallikrein 7


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure-based drug design to overcome species differences in kallikrein 7 inhibition of 1,3,6-trisubstituted 1,4-diazepan-7-ones.

Murafuji, H.Sugawara, H.Goto, M.Oyama, Y.Sakai, H.Imajo, S.Tomoo, T.Muto, T.

(2018) Bioorg Med Chem 26: 3639-3653

  • DOI: https://doi.org/10.1016/j.bmc.2018.05.044
  • Primary Citation of Related Structures:  
    5ZFH, 5ZFI

  • PubMed Abstract: 

    A series of 1,3,6-trisubstituted 1,4-diazepan-7-ones were prepared as kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme) inhibitors. Previously reported compounds 1-3 were potent human KLK7 inhibitors; however, they did not exhibit inhibitory activity against mouse KLK7. Comparison of the human and mouse KLK7 structures reveals the cause of this species differences; therefore, compounds that could inhibit both KLK7s were designed, synthesized, and evaluated. Through this structure-based drug design, compound 22g was identified as an inhibitor against human and mouse KLK7, and only one of the enantiomers, (-)-22g, exhibited potent inhibitory activity. Furthermore, the crystal structure of mouse KLK7 complexed with 22g enabled the elucidation of structure-activity relationships and justified 22g as a valuable compound to overcome the species differences.


  • Organizational Affiliation

    Asubio Pharma Co., Ltd., 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: murafuji.hidenobu.bj@daiichisankyo.co.jp.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Kallikrein-7224Mus musculusMutation(s): 0 
Gene Names: Klk7Prss6Scce
EC: 3.4.21.117
UniProt
Find proteins for Q91VE3 (Mus musculus)
Explore Q91VE3 
Go to UniProtKB:  Q91VE3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91VE3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.189 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.795α = 90
b = 71.795β = 90
c = 100.28γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2018-06-27 
  • Deposition Author(s): Sugawara, H.

Revision History  (Full details and data files)

  • Version 1.0: 2018-06-27
    Type: Initial release
  • Version 1.1: 2018-07-04
    Changes: Data collection, Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Refinement description