Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions.

Article Details

Citation

Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD

Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions.

J Med Chem. 2010 Jan 28;53(2):867-75. doi: 10.1021/jm901537q.

PubMed ID
20025281 [ View in PubMed
]
Abstract

This report demonstrates that solvent water relaxation measurements can be used for quantitative screening of ligand binding and for mechanistic investigations of enzymes containing paramagnetic metal centers by using conventional NMR instrumentation at high field. The method was exemplified using prolyl hydroxylase domain containing enzyme 2 (PHD2), a human enzyme involved in hypoxic sensing, with Mn(II) substituting for Fe(II) at the active site. K(D) values were determined for inhibitors that hinder access of water to the paramagnetic center. This technique is also useful for investigating the mechanism of suitable metalloenzymes, including order of ligand binding and modes of inhibition.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
FG-2216Egl nine homolog 1IC 50 (nM)73N/AN/ADetails