6HR3

Human Carbonic Anhydrase II in complex with 4-Propylbenzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.02 Å
  • R-Value Free: 0.145 
  • R-Value Work: 0.129 
  • R-Value Observed: 0.130 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.

Glockner, S.Ngo, K.Sager, C.P.Hufner-Wulsdorf, T.Heine, A.Klebe, G.

(2020) ACS Chem Biol 15: 675-685

  • DOI: 10.1021/acschembio.9b00895
  • Structures With Same Primary Citation

  • PubMed Abstract: 
  • Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from sur ...

    Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermodynamic and kinetic data from calorimetric titration measurements. The present study demonstrates the convenient collection of calorimetric data suitable for both thermodynamic and kinetic analysis for two series of congeneric ligands of human carbonic anhydrase II and correlates these findings with structural data obtained by macromolecular crystallography to shed light on the importance of shape complementarity for thermodynamics and kinetics governing a protein-ligand binding event. The study shows how minute chemical alterations change preferred ligand conformation and can be used to manipulate thermodynamic and kinetic signatures of binding. They give rise to the observation that analogous n -alkyl and n -alkyloxy derivatives of identical chain length swap their binding kinetic properties at unchanged binding affinity.


    Organizational Affiliation

    Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35032 Marburg, Germany.



Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Carbonic anhydrase 2
A
265Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1
Find proteins for P00918 (Homo sapiens)
Go to UniProtKB:  P00918
NIH Common Fund Data Resources
PHAROS  P00918
Small Molecules
Ligands 5 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
MBO
Query on MBO

Download CCD File 
A
MERCURIBENZOIC ACID
C7 H5 Hg O2
FVFZSVRSDNUCGG-UHFFFAOYSA-N
 Ligand Interaction
HG
Query on HG

Download CCD File 
A
MERCURY (II) ION
Hg
BQPIGGFYSBELGY-UHFFFAOYSA-N
 Ligand Interaction
4JE
Query on 4JE

Download CCD File 
A
4-propylbenzenesulfonamide
C9 H13 N O2 S
CICCMHNIYTXWRF-UHFFFAOYSA-N
 Ligand Interaction
BGC
Query on BGC

Download CCD File 
A
BETA-D-GLUCOSE
C6 H12 O6
WQZGKKKJIJFFOK-VFUOTHLCSA-N
 Ligand Interaction
ZN
Query on ZN

Download CCD File 
A
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.02 Å
  • R-Value Free: 0.145 
  • R-Value Work: 0.129 
  • R-Value Observed: 0.130 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.27α = 90
b = 41.519β = 104.59
c = 72.293γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing
Cootmodel building

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History 

  • Version 1.0: 2019-10-09
    Type: Initial release
  • Version 1.1: 2020-04-08
    Changes: Data collection, Database references