5LGO

Trypsin inhibitors for the treatment of pancreatitis - cpd 15


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.12 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Trypsin inhibitors for the treatment of pancreatitis.

Brandl, T.Simic, O.Skaanderup, P.R.Namoto, K.Berst, F.Ehrhardt, C.Schiering, N.Mueller, I.Woelcke, J.

(2016) Bioorg Med Chem Lett 26: 4340-4344

  • DOI: https://doi.org/10.1016/j.bmcl.2016.07.029
  • Primary Citation of Related Structures:  
    5LGO, 5LH4, 5LH8

  • PubMed Abstract: 

    Proline-based trypsin inhibitors occupying the S1-S2-S1' region were identified by an HTS screening campaign. It was discovered that truncation of the P1' moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile.


  • Organizational Affiliation

    Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland. Electronic address: trixi.brandl@novartis.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cationic 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
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
6VZ
Query on 6VZ

Download Ideal Coordinates CCD File 
D [auth A](2~{S},4~{S})-1-[4-(aminomethyl)-3-methoxy-phenyl]carbonyl-4-[4-(2-cyclopropylethoxy)-6,8-dihydro-5~{H}-pyrido[3,4-d]pyrimidin-7-yl]-~{N}-methyl-pyrrolidine-2-carboxamide
C27 H36 N6 O4
PZBPHXPZLFDRAP-REWPJTCUSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
B [auth A]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
CA
Query on CA

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

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.12 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.232α = 90
b = 55.232β = 90
c = 106.981γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-10
    Type: Initial release
  • Version 1.1: 2016-08-24
    Changes: Database references
  • Version 2.0: 2019-10-16
    Changes: Atomic model, Data collection