3WAB

Carboxypeptidase B in complex with DD2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.207 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural basis for inhibition of carboxypeptidase B by selenium-containing inhibitor: selenium coordinates to zinc in enzyme.

Yoshimoto, N.Itoh, T.Inaba, Y.Ishii, H.Yamamoto, K.

(2013) J Med Chem 56: 7527-7535

  • DOI: https://doi.org/10.1021/jm400816v
  • Primary Citation of Related Structures:  
    3WAB, 3WC5, 3WC6, 3WC7

  • PubMed Abstract: 

    Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) is a zinc-containing carboxypeptidase and significantly inhibits fibrinolysis. TAFIa inhibitors are thus expected to act as profibrinolytic agents. We recently reported the design and synthesis of selenium-containing inhibitors of TAFIa and their inhibitory activity. Here we report the crystal structures of potent selenium-, sulfur-, and phosphinic acid-containing inhibitors bound to porcine pancreatic carboxypeptidase B (ppCPB). ppCPB is a TAFIa homologue and is surrogate TAFIa for crystallographic analysis. Crystal structures of ppCPB complexed with selenium compound 1a, its sulfur analogue 2, and phosphinic acid derivative EF6265 were determined at 1.70, 2.15, and 1.90 Å resolution, respectively. Each inhibitor binds to the active site of ppCPB in a similar manner to that observed for previously reported inhibitors. Thus, in complexes, selenium, sulfur, and phosphinic acid oxygen coordinate to zinc in ppCPB. This is the first observation and report of selenium coordinating to zinc in CPB.


  • Organizational Affiliation

    High Technology Research Center, ‡Laboratory of Drug Design and Medicinal Chemistry and §Laboratory of Molecular and Cellular Pathophysiology, Showa Pharmaceutical University , 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carboxypeptidase B306Sus scrofaMutation(s): 0 
EC: 3.4.17.2
UniProt
Find proteins for P09955 (Sus scrofa)
Explore P09955 
Go to UniProtKB:  P09955
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09955
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
DDW PDBBind:  3WAB IC50: 34 (nM) from 1 assay(s)
BindingDB:  3WAB IC50: 3.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.207 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.314α = 90
b = 79.314β = 90
c = 100.342γ = 90
Software Package:
Software NamePurpose
d*TREKdata reduction
CNSrefinement
PDB_EXTRACTdata extraction
RAPID-AUTOdata collection
RAPID-AUTOdata reduction
d*TREKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-02
    Type: Initial release
  • Version 1.1: 2022-08-24
    Changes: Database references, Derived calculations
  • Version 1.2: 2023-11-08
    Changes: Data collection, Refinement description