7JL8

Human PrimPol extending from the correct primer base C opposite the 8-oxoguanine lesion

PDB DOI: https://doi.org/10.2210/pdb7JL8/pdb
NAKB: 7JL8

Classification: TRANSFERASE/DNA
Organism(s): Homo sapiens, synthetic construct
Expression System: Saccharomyces cerevisiae
Mutation(s): No

Deposited: 2020-07-29 Released: 2021-06-30
Deposition Author(s): Rechkoblit, O., Aggarwal, A.K.
Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.213
R-Value Work: 0.187
R-Value Observed: 0.188

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.

Rechkoblit, O., Johnson, R.E., Gupta, Y.K., Prakash, L., Prakash, S., Aggarwal, A.K.

(2021) Nat Commun 12: 4020-4020

PubMed: 34188055 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-021-24317-z
Primary Citation of Related Structures:
7JK1, 7JKL, 7JKP, 7JL8, 7JLG

PubMed Abstract:
PrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3'-terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)•A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3'-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.

Organizational Affiliation

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].

Macromolecule Content

Total Structure Weight: 102.33 kDa
Atom Count: 5,171
Modelled Residue Count: 560
Deposited Residue Count: 768
Unique protein chains: 1
Unique nucleic acid chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
DNA-directed primase/polymerase protein	A, D [auth B]	354	Homo sapiens	Mutation(s): 0 Gene Names: PRIMPOL, CCDC111 EC: 2.7.7 (PDB Primary Data), 2.7.7.102 (UniProt), 2.7.7.7 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q96LW4 (Homo sapiens) Explore Q96LW4 Go to UniProtKB: Q96LW4
PHAROS: Q96LW4 GTEx: ENSG00000164306
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q96LW4
Sequence Annotations Expand
Reference Sequence

Find similar nucleic acids by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Length	Organism	Image
DNA (5'-D(PAPTP(8OG)PCPCPTPAPCPCPAPCPA)-3')	B [auth C], E [auth G]	17	synthetic construct
Sequence Annotations Expand
Reference Sequence

Find similar nucleic acids by: Sequence | 3D Structure

Entity ID: 3
Molecule	Chains	Length	Organism	Image
DNA (5'-D(PGPTPGPGPTPAPGPGP*C)-3')	C [auth D], F [auth H]	13	synthetic construct
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
DTP Query on DTP Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain N [auth B] MOL2 format, chain G [auth A] MOL2 format, chain N [auth B] mmCIF format, chain G [auth A] mmCIF format, chain N [auth B]	G [auth A], N [auth B]	2'-DEOXYADENOSINE 5'-TRIPHOSPHATE C₁₀ H₁₆ N₅ O₁₂ P₃ SUYVUBYJARFZHO-RRKCRQDMSA-N		Interactions Focus chain G [auth A] Focus chain N [auth B] Interactions & Density Focus chain G [auth A] Focus chain N [auth B]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain K [auth A] SDF format, chain M [auth A] SDF format, chain T [auth B] MOL2 format, chain K [auth A] MOL2 format, chain M [auth A] MOL2 format, chain T [auth B] mmCIF format, chain K [auth A] mmCIF format, chain M [auth A] mmCIF format, chain T [auth B]	K [auth A], M [auth A], T [auth B]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain K [auth A] Focus chain M [auth A] Focus chain T [auth B] Interactions & Density Focus chain K [auth A] Focus chain M [auth A] Focus chain T [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain L [auth A] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain S [auth B] MOL2 format, chain I [auth A] MOL2 format, chain L [auth A] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] mmCIF format, chain I [auth A] mmCIF format, chain L [auth A] mmCIF format, chain Q [auth B] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B]	I [auth A], L [auth A], Q [auth B], R [auth B], S [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain L [auth A] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Interactions & Density Focus chain I [auth A] Focus chain L [auth A] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain J [auth A] MOL2 format, chain J [auth A] mmCIF format, chain J [auth A]	J [auth A]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Interactions & Density Focus chain J [auth A]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain O [auth B] SDF format, chain P [auth B] MOL2 format, chain H [auth A] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] mmCIF format, chain H [auth A] mmCIF format, chain O [auth B] mmCIF format, chain P [auth B]	H [auth A], O [auth B], P [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain O [auth B] Focus chain P [auth B] Interactions & Density Focus chain H [auth A] Focus chain O [auth B] Focus chain P [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.213
R-Value Work: 0.187
R-Value Observed: 0.188
Space Group: P 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 50.689	α = 68.47
b = 65.33	β = 85.67
c = 72.001	γ = 86.92

Software Package:

Software Name	Purpose
PHENIX	refinement
PDB_EXTRACT	data extraction
XDS	data reduction
XDS	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2021-06-30

Deposition Author(s):

Rechkoblit, O.

Aggarwal, A.K.

Funding Organization	Location	Grant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	United States	R35-GM131780

Revision History (Full details and data files)

Version 1.0: 2021-06-30
Type: Initial release
Version 1.1: 2021-07-14
Changes: Database references
Version 1.2: 2023-10-18
Changes: Data collection, Database references, Refinement description