4DTZ: Cytochrome P450 Bm3h-8c8 Mri Sensor Bound To Dopamine

Citation:
Abstract
New tools that allow dynamic visualization of molecular neural events are important for studying the basis of brain activity and disease. Sensors that permit ligand-sensitive magnetic resonance imaging (MRI) are useful reagents due to the noninvasive nature and good temporal and spatial resolution of MR methods. Paramagnetic metalloproteins can be effective MRI sensors due to the selectivity imparted by the protein active site and the ability to tune protein properties using techniques such as directed evolution. Here, we show that structure-guided directed evolution of the active site of the cytochrome P450-BM3 heme domain produces highly selective MRI probes with submicromolar affinities for small molecules. We report a new, high-affinity dopamine sensor as well as the first MRI reporter for serotonin, with which we demonstrate quantification of neurotransmitter release in vitro. We also present a detailed structural analysis of evolved cytochrome P450-BM3 heme domain lineages to systematically dissect the molecular basis of neurotransmitter binding affinity, selectivity, and enhanced MRI contrast activity in these engineered proteins.
PDB ID: 4DTZDownload
MMDB ID: 100526
PDB Deposition Date: 2012/2/21
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 1.55  Å
Source Organism:
Similar Structures:
Biological Unit for 4DTZ: monomeric; determined by author and by software (PISA)
Molecular Components in 4DTZ
Label Count Molecule
Protein (1 molecule)
1
Cytochrome P450 BM3 Variant 8C8
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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