Abstract
G protein-coupled receptor kinase 2 (GRK2) is a pharmaceutical target for the treatment of cardiovascular diseases such as congestive heart failure, myocardial infarction, and hypertension. To better understand how nanomolar inhibition and selectivity for GRK2 might be achieved, we have determined crystal structures of human GRK2 in complex with Gbetagamma in the presence and absence of the AGC kinase inhibitor balanol. The selectivity of balanol among human GRKs is assessed.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Azepines / chemistry*
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Crystallography, X-Ray
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
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G-Protein-Coupled Receptor Kinase 2 / antagonists & inhibitors
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G-Protein-Coupled Receptor Kinase 2 / chemistry*
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GTP-Binding Protein beta Subunits / chemistry*
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GTP-Binding Protein gamma Subunits / chemistry*
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Humans
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Hydroxybenzoates / chemistry*
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Models, Molecular*
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Phosphorylation
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Protein Binding
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Protein Conformation
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Tubulin / chemistry
Substances
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Azepines
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Hydroxybenzoates
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Tubulin
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ophiocordin
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Cyclic AMP-Dependent Protein Kinases
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GRK2 protein, human
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G-Protein-Coupled Receptor Kinase 2
Associated data
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PDB/3CIK
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PDB/3KRW
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PDB/3KRX