4Q4P

tRNA-Guanine Transglycosylase (TGT) in Complex with 2-{[2-(PIPERIDIN-1-YL)ETHYL]AMINO}-3,5-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.170 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.153 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Beyond Affinity: Enthalpy-Entropy Factorization Unravels Complexity of a Flat Structure-Activity Relationship for Inhibition of a tRNA-Modifying Enzyme.

Neeb, M.Betz, M.Heine, A.Barandun, L.J.Hohn, C.Diederich, F.Klebe, G.

(2014) J Med Chem 57: 5566-5578

  • DOI: https://doi.org/10.1021/jm5006868
  • Primary Citation of Related Structures:  
    4Q4O, 4Q4P, 4Q4Q, 4Q4R, 4Q4S

  • PubMed Abstract: 

    Lead optimization focuses on binding-affinity improvement. If a flat structure-activity relationship is detected, usually optimization strategies are abolished as unattractive. Nonetheless, as affinity is composed of an enthalpic and entropic contribution, factorization of both can unravel the complexity of a flat, on first sight tedious SAR. In such cases, the binding free energy of different ligands can be rather similar, but it can factorize into enthalpy and entropy distinctly. We investigated the thermodynamic signature of two classes of lin-benzopurines binding to tRNA-guanine transglycosylase. While the differences are hardly visible in the free energy, they involve striking enthalpic and entropic changes. Analyzing thermodynamics along with structural features revealed that one ligand set binds to the protein without inducing significant changes compared to the apo structure; however, the second series provokes complex adaptation, leading to a conformation similar to the substrate-bound state. In the latter state, a cross-talk between two pockets is suggested.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Queuine tRNA-ribosyltransferase386Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821Mutation(s): 0 
Gene Names: tgtZMO0363
EC: 2.4.2.29
UniProt
Find proteins for P28720 (Zymomonas mobilis subsp. mobilis (strain ATCC 31821 / ZM4 / CP4))
Explore P28720 
Go to UniProtKB:  P28720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28720
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2YO
Query on 2YO

Download Ideal Coordinates CCD File 
F [auth A]2-{[2-(piperidin-1-yl)ethyl]amino}-3,5-dihydro-8H-imidazo[4,5-g]quinazolin-8-one
C16 H20 N6 O
NFLZHTAOFKJMSG-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-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 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
E [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
2YO Binding MOAD:  4Q4P Kd: 407.4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.170 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.153 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.985α = 90
b = 64.853β = 93.32
c = 70.741γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data 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: 2014-07-09
    Type: Initial release
  • Version 1.1: 2014-07-23
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description