3WHW

MTH1 in complex with Ruthenium-based inhibitor

Summary for 3WHW

• Entry DOI: 10.2210/pdb3whw/pdb
• Related: 3ZR1
• Descriptor: 7,8-dihydro-8-oxoguanine triphosphatase, SULFATE ION, [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, ... (4 entities in total)
• Functional Keywords: mth1, organometallic inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Isoform p18: Cytoplasm. Isoform p26: Cytoplasm: P36639
• Total number of polymer chains: 2
• Total formula weight: 37834.55

Authors

Streib, M.,Kraeling, K.,Richter, K.,Steuber, H.,Meggers, E. (deposition date: 2013-09-03, release date: 2014-02-12, Last modification date: 2023-11-08)

Primary citation

Streib, M.,Kraeling, K.,Richter, K.,Xie, X.,Steuber, H.,Meggers, E.
An Organometallic Inhibitor for the Human Repair Enzyme 7,8-Dihydro-8-oxoguanosine Triphosphatase.
Angew.Chem.Int.Ed.Engl., 53:305-309, 2014

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.

PubMed: 24258965
DOI: 10.1002/anie.201307849

Experimental method

X-RAY DIFFRACTION (2.701 Å)