3WHW

MTH1 in complex with Ruthenium-based inhibitor

PDB DOI: https://doi.org/10.2210/pdb3WHW/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2013-09-03 Released: 2014-02-12
Deposition Author(s): Streib, M., Kraeling, K., Richter, K., Steuber, H., Meggers, E.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.70 ?
R-Value Free: 0.266
R-Value Work: 0.215
R-Value Observed: 0.217

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

An Organometallic Inhibitor for the Human Repair Enzyme 7,8-Dihydro-8-oxoguanosine Triphosphatase.

Streib, M., Kraeling, K., Richter, K., Xie, X., Steuber, H., Meggers, E.

(2014) Angew Chem Int Ed Engl 53: 305-309

PubMed: 24258965 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/anie.201307849
Primary Citation of Related Structures:
3WHW

PubMed Abstract:
The probe-based discovery of the first small-molecule inhibitor of the repair enzyme 8-oxo-dGTPase (MTH1) is presented, which is an unconventional cyclometalated ruthenium half-sandwich complex. The organometallic inhibitor with low-nanomolar activity displays astonishing specificity, as verified in tests with an extended panel of protein kinases and other ATP binding proteins. The binding of the organometallic inhibitor to MTH1 is investigated by protein crystallography.

Organizational Affiliation

Fachbereich Chemie, Philipps-Universit?t Marburg, Hans-Meerwein-Strasse, 35043 Marburg (Germany).

Macromolecule Content

Total Structure Weight: 37.83 kDa
Atom Count: 2,669
Modelled Residue Count: 308
Deposited Residue Count: 312
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
7,8-dihydro-8-oxoguanine triphosphatase	A, B	156	Homo sapiens	Mutation(s): 0 Gene Names: NUDT1, MTH1 EC: 3.6.1.55 (PDB Primary Data), 3.6.1.56 (PDB Primary Data), 3.6.1 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P36639 (Homo sapiens) Explore P36639 Go to UniProtKB: P36639
PHAROS: P36639 GTEx: ENSG00000106268
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P36639
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
RUX Query on RUX Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain K [auth B] MOL2 format, chain F [auth A] MOL2 format, chain K [auth B] mmCIF format, chain F [auth A] mmCIF format, chain K [auth B]	F [auth A], K [auth B]	[4-amino-2-methyl-6-(pyridin-2-yl-kappaN)quinazolin-7-yl-kappaC~7~](carbonyl){1-[(2,6-dimethoxyphenoxy)carbonyl]cyclopenta-2,4-dien-1-yl}ruthenium C₂₉ H₂₄ N₄ O₅ Ru AOUPQUZYXKBCEC-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain K [auth B] Interactions & Density Focus chain F [auth A] Focus chain K [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain J [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B]	C [auth A] D [auth A] E [auth A] G [auth B] H [auth B] C [auth A], D [auth A], E [auth A], G [auth B], H [auth B], I [auth B], J [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.70 ?
R-Value Free: 0.266
R-Value Work: 0.215
R-Value Observed: 0.217
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( ? )	Angle ( ? )
a = 59.76	α = 90
b = 67.65	β = 90
c = 79.54	γ = 90

Software Package:

Software Name	Purpose
MAR345	data collection
PHASER	phasing
PHENIX	refinement
XDS	data reduction
XDS	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-02-12

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-02-12
Type: Initial release
Version 1.1: 2017-11-22
Changes: Refinement description
Version 1.2: 2023-11-08
Changes: Data collection, Database references, Derived calculations, Refinement description

Prepare Data

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Deposit Data

Help and Resources

3WHW

MTH1 in complex with Ruthenium-based inhibitor

An Organometallic Inhibitor for the Human Repair Enzyme 7,8-Dihydro-8-oxoguanosine Triphosphatase.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)