SARS-CoV-2 gains entry into the body mainly via the lungs. After entering the blood, the virus rapidly multiplies to infect nearby cells. Endothelial cells line every blood vessel and have a surface area similar to a tennis court. These cells…
Blog Archives
Hot Topics: Trends in kinase drug discovery: twenty years of successfully targeting the kinome
The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology area and beyond. Continued advances in the molecular understanding of…
Hot Topics: Soluble ligands as drug targets
Historically, the main classes of drug targets have been receptors, enzymes, ion channels and transporters which are primarily targeted by small molecules. However, advances in molecular biology, genomics, and pharmacology have facilitated the development of different therapeutic modalities which in…
Hot Topics: TMEM163 regulates ATP-gated P2X receptor and behaviour
It is now clear that ligand-gated ion channels (LGICs) are not “stand alone” functional units, but form complexes with other components, including scaffolding proteins, regulatory proteins and enzymes. Besides their important physiological roles, these modulating proteins are also potential targets…
Hot Topics: Virtual screening on the crystal structure of the G protein-coupled melatonin MT1 receptor reveals several new chemical scaffolds with biological activity
Melatonin targets two high-affinity receptors, MT1 and MT2, that belong to the G protein-coupled receptor (GPCR) superfamily (1,2). Drugs acting on melatonin receptors are subscribed for circadian disorders (jet lag, shift work, etc.), insomnia and major depression (3). All marketed…
Hot Topics: Cardiac Ca2+ Channel Regulation in the Fight-or-Flight Response: the monomeric small G-protein as another piece in the puzzle
Thirty eight years after the discovery that injection of the catalytic subunits of cyclic AMP-dependent protein kinase A (PKA) into isolated pig ventricular cardiac myocytes (1) increases the amplitude of L-type Ca2+ current (today known to be formed by Cav1.2…
Hot Topics: Cryo-EM structure of a selective T-type calcium channel blocker bound to the Cav3.1 voltage-gated calcium channel
Nieng Yan’s group has now published the cryo-EM structure of the selective T-type Ca2+ channel blocker Z944 bound to the pore-forming α1-subunit of Cav3.1 T-type Ca2+ channels (1). This nicely adds to recent publications reporting of the high-resolution structures of…
Tagged with: calcium channel, hot topic, pharmacology, protein structure, VGICs, voltage-gated
Posted in Hot Topics
Posted in Hot Topics
Hot Topics: Deciphering the crystal structure of the leukotriene receptor CysLT2 opens up for improved therapeutics
Leukotrienes are lipid mediators of inflammation, initially recognized for their role in asthma, but also having potent effects in for example cardiovascular and neurological diseases as well as in cancer. The initial pharmacological classification of leukotriene receptors based on antagonist…
Hot Topics: New crystal structure of the muscarinic M5 receptor completes the set
Muscarinic receptors consist of 5 G protein-coupled receptors which along with nicotinic ion channels mediate the effects of acetylcholine. Despite years of research on the role of muscarinic receptors in the brain and periphery the Muscarinic M5 receptor has stood…
Hot Topics: 3D structure of the full-length P2X7 receptor provides insight into factors controlling agonist potency and receptor desensitisation
P2X receptors are ligand-gated cation channels for which ATP is the endogenous orthosteric agonist. Seven P2X subunits have been identified and they form trimers to produce at least twelve different receptor subtypes. The tertiary structure of several subtypes have been…
Hot Topics: Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel
In this report the Catterall laboratory succeeded in solving the high resolution structure of a voltage-gated Na+-channel (Nav) in its resting state (1). Why is this difficult and why is this important? It is difficult because Navs exist in the…
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