RCSB PDB - 6IPG: Post-catalytic Complex of Human DNA Polymerase Mu with Templating Cytosine and Mg-8oxodGMP

 6IPG

Post-catalytic Complex of Human DNA Polymerase Mu with Templating Cytosine and Mg-8oxodGMP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.62 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 

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Ligand Structure Quality Assessment 

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Literature

Human DNA Polymerase mu Can Use a Noncanonical Mechanism for Multiple Mn2+-Mediated Functions.

Chang, Y.K.Huang, Y.P.Liu, X.X.Ko, T.P.Bessho, Y.Kawano, Y.Maestre-Reyna, M.Wu, W.J.Tsai, M.D.

(2019) J Am Chem Soc 141: 8489-8502

  • DOI: https://doi.org/10.1021/jacs.9b01741
  • Primary Citation of Related Structures:  
    5ZLC, 6AEC, 6AEH, 6AK5, 6AK6, 6AK8, 6AK9, 6AKH, 6IPD, 6IPE, 6IPF, 6IPG, 6IPH, 6IPI, 6IPJ, 6IPK, 6IPL, 6IPM, 6IPN

  • PubMed Abstract: 

    Recent research on the structure and mechanism of DNA polymerases has continued to generate fundamentally important features, including a noncanonical pathway involving "prebinding" of metal-bound dNTP (MdNTP) in the absence of DNA. While this noncanonical mechanism was shown to be a possible subset for African swine fever DNA polymerase X (Pol X) and human Pol λ, it remains unknown whether it could be the primary pathway for a DNA polymerase. Pol μ is a unique member of the X-family with multiple functions and with unusual Mn 2+ preference. Here we report that Pol μ not only prebinds MdNTP in a catalytically active conformation but also exerts a Mn 2+ over Mg 2+ preference at this early stage of catalysis, for various functions: incorporation of dNTP into a single nucleotide gapped DNA, incorporation of rNTP in the nonhomologous end joining (NHEJ) repair, incorporation of dNTP to an ssDNA, and incorporation of an 8-oxo-dGTP opposite template dA (mismatched) or dC (matched). The structural basis of this noncanonical mechanism and Mn 2+ over Mg 2+ preference in these functions was analyzed by solving 19 structures of prebinding binary complexes, precatalytic ternary complexes, and product complexes. The results suggest that the noncanonical pathway is functionally relevant for the multiple functions of Pol μ. Overall, this work provides the structural and mechanistic basis for the long-standing puzzle in the Mn 2+ preference of Pol μ and expands the landscape of the possible mechanisms of DNA polymerases to include both mechanistic pathways.


  • Organizational Affiliation

    Institute of Biological Chemistry, Academia Sinica , 128 Academia Road Sec. 2 , Nankang, Taipei 115 , Taiwan.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed DNA/RNA polymerase mu356Homo sapiensMutation(s): 0 
Gene Names: POLMpolmu
EC: 2.7.7.7
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NP87 (Homo sapiens)
Explore Q9NP87 
Go to UniProtKB:  Q9NP87
PHAROS:  Q9NP87
GTEx:  ENSG00000122678 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NP87
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EPE
Query on EPE

Download Ideal Coordinates CCD File 
I [auth A]4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
PO4 (Subject of Investigation/LOI)
Query on PO4

Download Ideal Coordinates CCD File 
H [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
EDO
Query on EDO

Download Ideal Coordinates CCD File 
J [auth A],
K [auth A],
L [auth A],
M [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
MG (Subject of Investigation/LOI)
Query on MG

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
G [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.62 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.884α = 90
b = 68.403β = 90
c = 110.481γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted PO4Click on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-05-29
    Type: Initial release
  • Version 1.1: 2019-06-12
    Changes: Data collection, Database references
  • Version 1.2: 2024-03-27
    Changes: Data collection, Database references, Derived calculations