4JYT

Crystal Structure of Matriptase in complex with Inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors

Goswami, R.Mukherjee, S.Wohlfahrt, G.Ghadiyaram, C.Nagaraj, J.Chandra, B.R.Sistla, R.K.Satyam, L.K.Samiulla, D.S.Moilanen, A.Subramanya, H.S.Ramachandra, M.

(2013) ACS Med Chem Lett 4: 1152-1157

  • DOI: https://doi.org/10.1021/ml400213v
  • Primary Citation of Related Structures:  
    4JYT, 4JZ1, 4JZI

  • PubMed Abstract: 

    Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other serine proteases.


  • Organizational Affiliation

    Aurigene Discovery Technologies Limited , 39-40 KIADB Industrial Area, Electronic City Phase II, Bangalore 560 100, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Suppressor of tumorigenicity 14 protein241Homo sapiensMutation(s): 0 
Gene Names: ST14PRSS14SNC19TADG15
EC: 3.4.21.109
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y5Y6 (Homo sapiens)
Explore Q9Y5Y6 
Go to UniProtKB:  Q9Y5Y6
PHAROS:  Q9Y5Y6
GTEx:  ENSG00000149418 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y5Y6
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
N4A
Query on N4A

Download Ideal Coordinates CCD File 
B [auth A]4,4'-[{3-[(naphthalen-2-ylsulfonyl)amino]pyridine-2,6-diyl}bis(oxy)]dibenzenecarboximidamide
C29 H24 N6 O4 S
YVYNZHGMLLXWDD-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
N4A BindingDB:  4JYT Ki: 40 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.217 
  • Space Group: C 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.423α = 90
b = 140.658β = 90
c = 51.325γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
AMoREphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-19
    Type: Initial release
  • Version 1.1: 2015-02-25
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description