Hot topics in pharmacology

Recent publications of interest recommended by NC-IUPHAR

2017: Jan | Feb | Mar | Apr | May | June

June 2017

Comparative transcriptomics in human and mouse
(1) Breschi A et al. (2017). Comparative transcriptomics in human and mouse. Nat Rev Genet, 18(7):425-440. [PMID:28479595]

An Expanded View of Complex Traits: From Polygenic to Omnigenic
(1) Boyle EA et al. (2017). An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell, 169(7):1177-1186. [PMID:28622505]

Structural basis for the cooperative allosteric activation of the free fatty acid receptor GPR40
(1) Lu J et al. (2017). Structural basis for the cooperative allosteric activation of the free fatty acid receptor GPR40. Nat Struct Mol Biol., doi: 10.1038/nsmb.3417. [Epub ahead of print] [PMID:28581512]

Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A
(1) Paulino C et al. (2017). Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A. Elife, 6: e26232. [PMID:28561733]


Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474

Comments by Chris Southan (@cdsouthan)

The historical context for this commentary can be found in this blogpost. This latest report, based on activity-based profiling (ABPP), constitutes the first open biochemical investigation of BIA 10-2474 (1). The ABPP results show it inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. In addition BIA 10-2474 (but not PF04457845) produced substantial alterations in lipid networks in human cortical neurons. The authors are appropriately cautious in not over-extrapolating their findings to causality of pathology recorded in the unfortunate patients (see clinical report in PMID 27806235). However, biochemical and pharmacological questions still remain. One of these is that, given the initial binding interaction is no less than three orders of magnitude lower that PF004457845, it's not entirely clear why 10-2474 was chosen as the lead. Another question is the basic kinetic parameters for purified enzymes (not just crude cell extracts in vitro) are still not available. This should include at least two methods for confirming irreversibility (e.g. IC50 vs pre-incubation or using a 10-2474 radiolabeled derivative). Word has it that a BIAL paper is in preparation so this aspect might be addressed by new results. Note also there are now two compound suppliers in PubChem offering BIA 10-2474 so more experimental reports could be expected.

The GtoPdb entries below have been updated with key interactions from this paper and will go live at the next release.
BIA 10-2474
PF004457845
FAAH
FAAH2

(1) van Esbroeck ACM et al. (2017). Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474. Science, 356(6342): 1084-1087 [PMID:28596366]


Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect?
(1) Welsh P et al. (2017). Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect? Br J Pharmacol., doi: 10.1111/bph.13818. [Epub ahead of print] [PMID:28409825]

GDF15 is a heart‐derived hormone that regulates body growth
(1) Wang T et al. (2017). GDF15 is a heart‐derived hormone that regulates body growth. EMBO Mol Med., doi: 10.15252/emmm.201707604. [Epub ahead of print] [PMID:28572090]


GPR3 and GPR6, novel molecular targets for cannabidiol

Comments by Steve Alexander (@mqzspa)

Cannabidiol is a major metabolite from the Cannabis plant, although levels vary dependent on genetic, regional, cultivation and other factors. It lacks the psychotropic nature of THC, but has been reported to have many biological effects, to the extent that clinical trials for infantile intractable epilepsy are currently ongoing in the US. GPR3 and GPR6 are orphan GPCRs, which have previously been reported to elevate cAMP levels constitutively when expressed in recombinant systems. Although there was some evidence for activation by sphingosine 1-phosphate, this was not reproduced. In this report, a number of endogenous and Cannabis-derived metabolites were examined for their effects on β-arrestin2 recruitment in cells expressing either GPR3 or GPR6. Of these agents, only CBD caused a reduction in β-arrestin2 recruitment in a concentration-dependent manner, with pIC50 values of 5.9 and 6.7 at GPR3 and GPR6, respectively. The authors suggest that the inverse agonist nature of CBD at these receptors might be of relevance for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s Disease. Read the full article on our blog

(1) Laun AS, Song ZH. (2017) GPR3 and GPR6, novel molecular targets for cannabidiol. Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2017.05.165. [Epub ahead of print] [PMID:28571738]


Crystal structure of the GLP-1 receptor bound to a peptide agonist.
(1) Jazayeri A et al. (2017). Crystal structure of the GLP-1 receptor bound to a peptide agonist. Nature, doi: 10.1038/nature22800. [Epub ahead of print] [PMID:28562585]

Identification of the gene that codes for the σ2 receptor
(1) Alon A et al. (2017). Identification of the gene that codes for the σ2 receptor. Proc Natl Acad Sci U S A., doi: 10.1073/pnas.1705154114. [Epub ahead of print] [PMID:28559337]


May 2017

Structure of the human multidrug transporter ABCG2.
(1) Taylor NMI et al. (2017). Architecture of the human interactome defines protein communities and disease networks. Nature, 2017 May 29. doi: 10.1038/nature22345. [Epub ahead of print] [PMID:28554189].

Microbiota in T-cell homeostasis and inflammatory diseases
(1) Lee N. & Kim W-U. (2017). Microbiota in T-cell homeostasis and inflammatory diseases. Experimental & Molecular Medicine, 49, e340; doi:10.1038/emm.2017.36. [Full text].

Architecture of the human interactome defines protein communities and disease networks
(1) Huttlin E.L. et al. (2017). Architecture of the human interactome defines protein communities and disease networks. Nature, 545(7655):505-509. [PMID:28514442].

Structural Basis for Apelin Control of the Human Apelin Receptor
(1) Ma Y et al. (2017). Structural Basis for Apelin Control of the Human Apelin Receptor. Structure, doi: 10.1016/j.str.2017.04.008. [Epub ahead of print]. [PMID:28528775].

Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein
(1) Zhang Y et al. (2017). Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature, doi:10.1038/nature22394. [Epub ahead of print]. [Full text].


Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand

Comments by Shane C. Wright, Gunnar Schulte (Karolinska Institutet)

The recently published structure of a full-length SMO bound to the stabilizing compound TC114 builds on emerging concepts from earlier crystal structures of SMO and provides novel insight into how structural rearrangements of the CRD relative to the receptor core coordinate receptor activation while relating this to WNT receptors [1]. Read the full article on our blog

(1) Zhang X et al. (2017). Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand. Nat Commun., 8:15383. [PMID:28513578].


Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators

Comments by Patrick Sexton (Monash University, Melbourne)

The glucagon-like peptide-1 receptor (GLP-1R) is a major target for treatment of Type 2 diabetes but has been refractory to the development of small molecule compounds as potential therapeutics. Song et al., (1) report the first crystal structures of the GLP-1R transmembrane domain in complex with 2 distinct negative allosteric modulators (NAMs) (PF-06372222 and NNC0640). Read the full article on our blog

(1) Song G et al. (2017). Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature, doi: 10.1038/nature22378. [Epub ahead of print]. [PMID:28514449].


Structure of the full-length glucagon class B G-protein-coupled receptor

Comments by Laurence J. Miller (Mayo Clinic, Scottsdale, AZ, USA)

Zhang et al. (1) now report a crystal structure of full length glucagon receptor (GCGR) in an inactive conformation stabilized by the non-peptidyl antagonist, NNC0640, and mAb1, bound to the ECD. In this new structure, the ECD is elongated above the TMD, with mAb1 resting on extracellular loop 1 (ECL1), and with the stalk region that links the two dominant receptor domains present in a β-strand conformation lying across the helical bundle between ECL1 and ECL2/ECL3. Read the full article on our blog

(1) Zhang H et al. (2017). Structure of the full-length glucagon class B G-protein-coupled receptor. Nature, doi: 10.1038/nature22363. [Epub ahead of print]. [PMID:28514451].


Selectivity determinants of GPCR–G-protein binding

Comments by Chris Southan (@cdsouthan)

As a detailed comparative sequence/structure/evolution analysis it is relatively unusual (in a good sense) to see such a bioinformatics article in Nature. This tour de force was a collaboration between MRC Laboratory of Molecular Biology, Cambridge UK and the Department of Drug Design and Pharmacology, University of Copenhagen (home of the GPCRdb team). As we know, GPCR signal transduction involves the binding of ligand-activated receptors to their appropriate Gα proteins. In this work selectivity-determining positions for signal transduction (as structural "barcodes") were inferred by comprehensively comparing the sequence conservation between paralogues and orthologues, incorporating information from recent structures. The residue positions for the interaction interfaces are collated and presented at gpcrdb.org (tab ‘Signal Proteins’) for all human receptors and their 16 Gα proteins. This will be updated (including data from new structures) as a guide to interface determinants of coupling selectivity. Many applications of this resource can be envisaged. These could include: exploring options to target GPCR-G protein interfaces with agents that block coupling between the receptor and G protein intracellularly, protein engineering, structural studies and understanding the consequences of natural variation or rare disease associated mutations occurring in the vicinity of the barcode positions.

Note that all GtoPdb GPCRs have cross-references to GPCRdb (who we collaborate with) so users can navigate structural data (including the barcode positions) via GPCRdb, but also exploit ligand-centric navigation via GtoPdb and links out to genomic variants via the Ensembl links. Read the full article on our blog

(1) Flock et al. (2017). Selectivity determinants of GPCR-G-protein binding. Nature545: 317-322. [PMID:28489817].


Protein-phospholipid interplay revealed with crystals of a calcium pump

Comments by Steve Alexander (@mqzspa)

Norimatsu and colleagues [1] have used X-ray solvent contrast modulation to assess density maps of four activation statses of SERCA1. Their observations suggest an unexpected movement of the transporter core, which allows an exaggerated ‘waving’ of the cytoplasmic-extended calcium-binding domain during the cycle of calcium transport. Read the full article on our blog

(1) Norimatsu et al. (2017). Protein-phospholipid interplay revealed with crystals of a calcium pump. Nature, 545(7653):193-198. [PMID:28467821].


Consequences Of Natural Perturbations In The Human Plasma Proteome
(1) Sun et al. (2017). Consequences Of Natural Perturbations In The Human Plasma Proteome. bioRxiv, doi:10.1101/134551. [bioRxiv: 134551].


Assessment of the significance of patent-derived information for the early identification of compound–target interaction hypotheses
(1) Senger, S. (2017). Assessment of the significance of patent-derived information for the early identification of compound–target interaction hypotheses. Journal of Chemoinformatics, 9:26, doi: 10.1186/s13321-017-0214-2. [SpringerOpen: view article].


A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures
(1) Wong et al. (2017). A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures. Immunity, 45(2):442-5. [PMID: 27521270].


April 2017

New developments in cryo-electron microscopy reveal the first Class B GPCR active structure in complex with a G protein

Comments by Dr. Fiona H. Marshall (Director & CSO, Heptares Therapeutics) (@aston_fm)

Solving fully active structures in complex with G proteins is challenging. Recent advances in cryo-electron microscopy (cryo-EM) mean that near atomic resolution is becoming possible for protein complexes of smaller molecular size (sub 100kDa). Using the volta phase plate greatly increases the contrast, particularly at the lower end of the molecular size range, meaning that structures of GPCR complexes are now within reach. The first example of this has been published [1]. Read the full article on our blog

(1) Liang et al. (2017). Phase-plate cryo-EM structure of a class B GPCR–G-protein complex. Nature, doi: 10.1038/nature22327. [PMID: 28437792].


Last rolls of the yoyo: Assessing the human canonical protein count
(1) Southan, C. (2017). Last rolls of the yoyo: Assessing the human canonical protein count. F1000Research, 6:448. [F1000: doi:10.12688/f1000research.11119.1].


Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity
(1) Saleheen et al. (2017). Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. Nature, 544(7649):235-239. [PMID: 28406212].


The Drug Repurposing Hub: a next-generation drug library and information resource
(1) Corsello et al. (2017). The Drug Repurposing Hub: a next-generation drug library and information resource. Nat. Med., 23(4):405-408. [PMID: 28388612].


Neurokinin 3 receptor antagonism for menopausal hot flushes

Comments by Chris Southan (@cdsouthan)

Neurokinin B signalling is increased in menopausal women and has been implicated as an important mediator of hot flushes. A phase 2 trial has assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901 (AZD2624)) [1]. Read the full article on our blog

(1) Prague et al. (2017). Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet, S0140-6736(17)30823-1. [PMID: 28385352].


Fish peptide treats cardiovascular disease

Comments by Chris Southan (@cdsouthan)

The novel GPCR peptide ligand Elabela/Toddler (APELA, Ela), first identified in the fish Danio and critical for the development of the heart, has now been identified in the human cardiovascular system. Yang et al. [1] have recently showed that the peptide binds to the apelin receptor in human heart. Read the full article on our blog

(1) Yang et al. (2017). Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension. Circulation, 135(12):1160-1173. [PMID: 28137936].


Crystal structures of human AT2 reveal molecular mechanism for lack of desensitization and internalization

Comments by Anthony Davenport

The intracellular signal transduction processes activated by the angiotensin AT2 receptor, are atypical for a GPCR and different from the AT1 receptor. Although the classic motifs a GPCR are present in AT2 receptor; it fails to demonstrate classic features of G-protein signalling such as desensitization by phosphorylation, and receptor regulation by internalization. Zhang et al. [1] report the crystal structures of human AT2 bound to an AT2-selective ligand and to an AT1 /AT2 dual ligand, capturing the receptor in an active-like conformation. Read the full article on our blog

(1) Zhang et al. (2017). Structural basis for selectivity and diversity in angiotensin II receptors. Nature, 544(7650):327-332. [PMID: 28379944].


The druggable genome and support for target identification and validation in drug development (3rd Apr 2017)
(1) Finan et al. (2017). The druggable genome and support for target identification and validation in drug development. Science Translational Medicine, 29(383) eaag1166. [Science Trans Med: Full text].


March 2017

FDA allows marketing of tests to provide genetic risk information
The FDA approved genetic testing company 23andMe to sell customers their susceptibility to heritable genetic traits. Many of these are pharmacologically revelevant

FDA news release


Structural insights into adiponectin receptors suggest ceramidase activity

Comments by Steve Alexander (@mqzspa)

Adiponectin receptors, Adipo1 and Adipo2 suggested to exhibit ceramidase activity - based on in silico evidence [1]. Read the full article on our blog

(1) Vasiliauskaité-Brooks et al. (2017). Structural insights into adiponectin receptors suggest ceramidase activity. Nature, 544(7648):120-123. [PMID: 28329765].


Molecular Structure of the Human CFTR Ion Channel
(1) Liu et al. (2017). Molecular Structure of the Human CFTR Ion Channel. Cell, 23;169(1):85-95. [PMID: 28340353].


Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research
(1) Manolio et al. (2017). Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research. Cell, 169(1):6-12. [PMID: 28340351].


Drug Target Ontology to Classify and Integrate Drug Discovery Data
(1) Lin et al. (2017). Drug Target Ontology to Classify and Integrate Drug Discovery Data. bioRxiv, doi:10.1101/117564. [bioRxiv: 117564].


Functional Social network architecture of human immune cells unveiled by quantitative proteomics
(1) Rieckmann et al. (2017). Social network architecture of human immune cells unveiled by quantitative proteomics. Nat. Immunol., 18(5):583-593. [PMID: 28263321].


Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation
(1) Kim et al. (2017). Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation. Cell, 168(6):1053-1064. [PMID: 28283061].


An atlas of human long non-coding RNAs with accurate 5′ ends
(1) Hon et al. (2017). An atlas of human long non-coding RNAs with accurate 5′ ends. Nature, 543(7744):199-204. [PMID: 28241135].


The Ecstacy and Agony of Assay Interference Compounds
(1) Alrich et al. (2017). The Ecstacy and Agony of Assay Interference Compounds. Biochemistry, 56(10):1363-1366. [PMID: 28244742].


Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1

Comments by Prof. Ian Kerr (University of Nottingham) (@iankerr_science)

Despite a flurry of mammalian ATP binding cassette (ABC) transporter structures in the last 2 years the Holy Grail has still been to determine how these diverse proteins interact with their transport substrates. Jue Chen and colleagues at the Rockefeller have now accomplished this for the multidrug resistance protein-1 (MRP1/ABCC1) using advances in high resolution cryo-electron microscopy to show the structures of substrate-free and leukotriene C4 bound protein [1]. Read the full article on our blog

(1) Johnson Z.L., Chen J. (2016). Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1. Cell, 9;168(6):1075-1085.e9. [PMID: 28238471].


The complete structure of an activated open sodium channel
(1) Sula et al. (2017). The complete structure of an activated open sodium channel. Nat. Commun., 8:14205. [PMID: 28205548].


Peripherally administered orexin improves survival of mice with endotoxin shock
(1) Ogawa et al. (2017). Peripherally administered orexin improves survival of mice with endotoxin shock. Elife, 30;5. [PMID: 28035899].


Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling
(1) Alvarez-Curto et al. (2017). Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling. J. Biol. Chem., 291(53):27147-27159. [PMID: 27852822].


Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity
(1) Glukhova et al. (2017). Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity Cell, 168(5):867-877. [PMID: 28235198].


The Orphan Receptor GPR17 Is Unresponsive to Uracil Nucleotides and Cysteinyl Leukotrienes
(1) Simon et al. (2017). The Orphan Receptor GPR17 Is Unresponsive to Uracil Nucleotides and Cysteinyl Leukotrienes. Mol. Pharmacol., 91(5):518-532. [PMID: 28254957].


Pharmacology of Modulators of Alternative Splicing
(1) Bates et al. (2017). Pharmacology of Modulators of Alternative Splicing. Pharmacol. Rev., 69(1):63-79. [PMID: 28034912].


Ligand and Target Discovery by Fragment-Based Screening in Human Cells
(1) Parker et al. (2017). Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell, 168(3):527-541. [PMID: 28111073].


Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin
(1) Metcalf et al. (2017). Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin. ACS Med. Chem. Lett., 8(3):321-326. [PMID: 28337324].


Crystal Structure of an LSD-Bound Human Serotonin Receptor
(1) Wacker et al. (2017). Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell, 168(3):377-389. [PMID: 28129538].


Structures of the Human HCN1 Hyperpolarization-Activated Channel
(1) Lee C.H. & MacKinnon R. (2017). Structures of the Human HCN1 Hyperpolarization-Activated Channel. Cell, 168(1-2):111-120. [PMID: 28086084].


Structure of a Pancreatic ATP-Sensitive Potassium Channel
(1) Li et al. (2017). Structure of a Pancreatic ATP-Sensitive Potassium Channel. Cell, 168(1-2):101-110. [PMID: 28086082].


February 2017

A global genetic interaction network maps a wiring diagram of cellular function
(1) Costanzo et al. (2016). A global genetic interaction network maps a wiring diagram of cellular function. Science, 353(6306). [PMID: 27708008].


Orphan receptor ligand discovery by pickpocketing pharmacological neighbors
(1) Ngo et al. (2017). Orphan receptor ligand discovery by pickpocketing pharmacological neighbors. Nat. Chem. Biol., 13(2):235-242. [PMID: 27992882].


Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists
(1) Zheng et al. (2016). Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists. Nature, 540(7633):458-461. [PMID: 27926736].


Intracellular allosteric antagonism of the CCR9 receptor
(1) Oswal et al. (2016). Intracellular allosteric antagonism of the CCR9 receptor. Nature, 540(7633):462-465. [PMID: 27926729].


Visualizing GPCR ‘Megaplexes’ Which Enable Sustained Intracellular Signaling
(1) Marshall F. H. (2016). Visualizing GPCR ‘Megaplexes’ Which Enable Sustained Intracellular Signaling. Trends Biochem Sci, 41(12):985-986. [PMID: 27825513].


Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2
Guide to Pharmacology: Ryanodine receptor family
(1) Peng et al. (2016). Novel agonist bioisosteres and common structure-activity relationships for the orphan G protein-coupled receptor GPR139. Sci. Rep., 6, 36681. [PMID: 27830715].


January 2017

The orphan GPR139 receptor is activated by peptides

Comments by David E. Gloriam and Anne Cathrine Nøhr Jensen (Department of Drug Design and Pharmacology, University of Copenhagen)

Two new publications on the orphan class A GPCR, GPR139. The first describing the first combined structure-activity relationships of all surrogate agonists, and a common pharmacophore model for future ligand identification and optimization [1]. The second, showing that the endogenous melanocortin 4 receptor agonists,; adrenocorticotropic hormone and α- and β-melanocyte stimulating hormone in the low micromolar range. In addition, a potentially novel subpeptide (from consensus cleavage site) represents the most potent putative endogenous activator, so far (EC50 value of 600 nM) [2]. Read the full article on our blog

(1) Shehata, M.A. (2016). Novel agonist bioisosteres and common structure-activity relationships for the orphan G protein-coupled receptor GPR139. Sci. Rep., 6, 36681. [PMID: 27830715].

(2) Nøhr, A.C. et al. (2016). The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW. Neurochem Int., 102:105-113. [PMID: 27916541].


X-ray crystallographic study defines binding domains for Ca2+ antagonist drugs and their molecular mechanism of action

Comments by Jörg Striessnig (Department of Pharmacology and Toxicology – Institute of Pharmacy, Universität Innsbruck)

This year witnessed a tremendous progress in our understanding of the structure-function relationship of voltage-gated Ca2+ channels. This is based on the cryo-electron microscopy structure of the rabbit Cav1.1 Ca2+ channel complex at a nominal resolution of 3.6 Å (see Hot Topics Sep 20, 2016) which is now nicely complemented by a study defining the binding domains for Ca2+ antagonist drugs and their molecular mechanism of action at atomic resolution [1]. Read the full article on our blog

(1) Tang et al. (2016). Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs. Nature, 537, 117–121. [PMID: 27556947].


Archive of previous years