4RT2

Ternary complex crystal structure of DNA polymerase Beta with (alpha,beta)-CH2-(beta,gamma)-NH-dTTP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.92 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.179 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Two Scaffolds from Two Flips: (alpha, beta)/(beta, gamma) CH2/NH "Met-Im" Analogues of dTTP.

Kadina, A.P.Kashemirov, B.A.Oertell, K.Batra, V.K.Wilson, S.H.Goodman, M.F.McKenna, C.E.

(2015) Org Lett 17: 2586-2589

  • DOI: https://doi.org/10.1021/acs.orglett.5b00799
  • Primary Citation of Related Structures:  
    4RT2, 4RT3

  • PubMed Abstract: 

    Novel α,β-CH2 and β,γ-NH (1a) or α,β-NH and β,γ-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase β, attributed to an NH-group interaction with R183 in the active site.


  • Organizational Affiliation

    †Department of Chemistry, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA polymerase beta335Homo sapiensMutation(s): 0 
Gene Names: POLB
EC: 2.7.7.7 (PDB Primary Data), 4.2.99 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P06746 (Homo sapiens)
Explore P06746 
Go to UniProtKB:  P06746
PHAROS:  P06746
GTEx:  ENSG00000070501 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06746
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*CP*CP*GP*AP*CP*AP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3')B [auth T]16synthetic construct
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*(DOC))-3')C [auth P]10synthetic construct
Sequence Annotations
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  • Reference Sequence

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Entity ID: 4
MoleculeChains LengthOrganismImage
DNA (5'-D(P*GP*TP*CP*GP*G)-3')5synthetic construct
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
N6T
Query on N6T

Download Ideal Coordinates CCD File 
J [auth A]2'-deoxy-5'-O-[(S)-hydroxy{[(S)-hydroxy(phosphonoamino)phosphoryl]methyl}phosphoryl]-3,4-dihydrothymidine
C11 H20 N3 O12 P3
FTYKINXQGSFHAF-DJLDLDEBSA-N
CL
Query on CL

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I [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG
Query on MG

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E [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
NA
Query on NA

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F [auth A],
G [auth A],
H [auth A]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.92 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.179 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.587α = 90
b = 79.409β = 107.27
c = 55.315γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-01
    Type: Initial release
  • Version 1.1: 2017-11-22
    Changes: Refinement description
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description