4P10

pro-carboxypeptidase U In Complex With 5-(3-aminopropyl)-1-propyl-6,7-dihydro-4H-benzimidazole-5-carboxylic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.186 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa).

Brink, M.Dahlen, A.Olsson, T.Polla, M.Svensson, T.

(2014) Bioorg Med Chem 22: 2261-2268

  • DOI: https://doi.org/10.1016/j.bmc.2014.02.010
  • Primary Citation of Related Structures:  
    4P10

  • PubMed Abstract: 

    A series of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid and 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid derivatives designed as inhibitors of TAFIa has been prepared via a common hydrogenation-alkylation sequence starting from the appropriate benzimidazole and imidazopyridine system. We present a successful design strategy using a conformational restriction approach resulting in potent and selective inhibitors of TAFIa. The X-ray structure of compound 5 in complex with a H333Y/H335Q double mutant TAFI indicate that the conformational restriction is responsible for the observed potency increase.


  • Organizational Affiliation

    Cardiovascular and Metabolic Disorders Research Area, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carboxypeptidase B2404Homo sapiensMutation(s): 2 
Gene Names: CPB2
EC: 3.4.17.20
UniProt & NIH Common Fund Data Resources
Find proteins for Q96IY4 (Homo sapiens)
Explore Q96IY4 
Go to UniProtKB:  Q96IY4
PHAROS:  Q96IY4
GTEx:  ENSG00000080618 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96IY4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2B8
Query on 2B8

Download Ideal Coordinates CCD File 
B [auth A](5R)-5-(3-aminopropyl)-1-propyl-4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid
C14 H23 N3 O2
DPDWQELEXVLQSO-CQSZACIVSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
DMS
Query on DMS

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

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
2B8 BindingDB:  4P10 IC50: min: 8, max: 1000 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.186 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.576α = 90
b = 49.243β = 93.12
c = 95.048γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata 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: 2014-08-13
    Type: Initial release
  • Version 1.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary