6QFV

Human carbonic anhydrase II with bound IrCp* complex (cofactor 8) to generate an artificial transfer hydrogenase (ATHase)

  • Classification: OXIDOREDUCTASE
  • Organism(s): Homo sapiens
  • Expression System: Escherichia coli
  • Mutation(s): No 

  • Deposited: 2019-01-10 Released: 2019-04-17 
  • Deposition Author(s): Rebelein, J.G.
  • Funding Organization(s): Swiss National Science Foundation, European Research Council, European Molecular Biology Organization

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.167 
  • R-Value Work: 0.156 
  • R-Value Observed: 0.157 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Chemical Optimization of Whole-Cell Transfer Hydrogenation Using Carbonic Anhydrase as Host Protein.

Rebelein, J.G.Cotelle, Y.Garabedian, B.Ward, T.R.

(2019) ACS Catal 9: 4173-4178

  • DOI: https://doi.org/10.1021/acscatal.9b01006
  • Primary Citation of Related Structures:  
    6QFU, 6QFV, 6QFW, 6QFX

  • PubMed Abstract: 

    Artificial metalloenzymes combine a synthetic metallocofactor with a protein scaffold and can catalyze abiotic reactions in vivo . Herein, we report on our efforts to valorize human carbonic anhydrase II as a scaffold for whole-cell transfer hydrogenation. Two platforms were tested: periplasmic compartmentalization and surface display in Escherichia coli . A chemical optimization of an IrCp* cofactor was performed. This led to 90 turnovers in the cell, affording a 69-fold increase in periplasmic product formation over the previously reported, sulfonamide-bearing IrCp* cofactor. These findings highlight the versatility of carbonic anhydrase as a promising scaffold for whole-cell catalysis with artificial metalloenzymes.


  • Organizational Affiliation

    Department of Chemistry, University of Basel, BPR 1096, Mattenstrasse 24a, 4058 Basel, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens)
Explore P00918 
Go to UniProtKB:  P00918
PHAROS:  P00918
GTEx:  ENSG00000104267 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00918
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
J0N (Subject of Investigation/LOI)
Query on J0N

Download Ideal Coordinates CCD File 
B [auth A]4-[2-(9-chloranyl-2',3',4',5',6'-pentamethyl-7-oxidanylidene-spiro[1$l^{4},8-diaza-9$l^{8}-iridabicyclo[4.3.0]nona-1(6),2,4-triene-9,1'-1$l^{8}-iridapentacyclo[2.2.0.0^{1,3}.0^{1,5}.0^{2,6}]hexane]-8-yl)ethyl]benzenesulfonamide
C24 H29 Cl Ir N3 O3 S
GPKFYIUARYJGFU-UHFFFAOYSA-L
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SO4 BindingDB:  6QFV Ki: min: 8.90e+7, max: 3.00e+8 (nM) from 4 assay(s)
J0N Binding MOAD:  6QFV Kd: 49 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.167 
  • R-Value Work: 0.156 
  • R-Value Observed: 0.157 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.396α = 90
b = 41.68β = 104.4
c = 72.353γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland200020_162348
European Research CouncilDrEAM
Swiss National Science FoundationSwitzerlandNCCR MSE
European Molecular Biology OrganizationGermanyALTF 194-2017

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-17
    Type: Initial release
  • Version 1.1: 2019-05-22
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Refinement description