Abstract：
:Chemokine receptors belong to the class A of G protein-coupled receptors (GPCRs) and are implicated in a wide variety of physiologic functions, mostly related to the homeostasis of the immune system. Chemokine receptors are also involved in multiple pathologic processes, including immune and autoimmune diseases, as well as cancer. Hence, several members of this GPCR subfamily are considered to be very relevant therapeutic targets. Since drug discovery efforts can be significantly reinforced by the availability of crystal structures, substantial efforts in the area of chemokine receptor structural biology could dramatically increase the outcome of drug discovery campaigns. This short review summarizes the available data on chemokine receptor crystal structures, discusses the numerous applications from chemokine receptor structures that can enhance the daily work of molecular pharmacologists, and describes the challenges and pitfalls to consider when relying on crystal structures for further research applications. SIGNIFICANCE STATEMENT: This short review summarizes the available data on chemokine receptor crystal structures, discusses the numerous applications from chemokine receptor structures that can enhance the daily work of molecular pharmacologists, and describes the challenges and pitfalls to consider when relying on crystal structures for further research applications.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Arimont M,Hoffmann C,de Graaf C,Leurs Rdoi
10.1124/mol.119.117168subject
Has Abstractpub_date
2019-12-01 00:00:00pages
765-777issue
6eissn
0026-895Xissn
1521-0111pii
mol.119.117168journal_volume
96pub_type
杂志文章,评审abstract：:The in vivo bioavailability of exogenous fibroblast growth factor 2 (FGF2) was studied after i.v. injection of uniformly 14C-labeled FGF2 into young rats. 14C-FGF2 was rapidly accumulated in almost all solid organs within 5 min. After 30 min, more than 65% of FGF2 was retained in liver, 4.5% in kidneys, 1.2% in spleen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.1.74
更新日期：1999-01-01 00:00:00
abstract：:Expression vectors were designed and constructed to achieve optimum production of two different isozymes of rat glutathione S-transferase (GST) (EC 2.5.1.18) in COS cells, for studies of drug resistance. Promoter-enhancer elements from the simian virus 40 (SV40) early-region or the mouse alpha 2(I)-collagen gene, GST ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:The mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in intracellular signaling, and this cascade may impinge on cAMP response elements (CREs) of target genes. Both the MAPK pathway and chromogranin A expression may be activated by cytosolic calcium influx, and calcium-dependent signals map onto th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.1.59
更新日期：1998-07-01 00:00:00
abstract：:Thymidine phosphorylase (TPase) is one of the key enzymes involved in the pyrimidine nucleoside salvage pathway. However, TPase also stimulates angiogenesis, and its expression correlates well with microvessel density and metastasis in a variety of human tumors. We have shown recently that 5'-O-trityl-inosine (KIN59) ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.021188
更新日期：2006-08-01 00:00:00
abstract：:Prokaryotes produce a variety of toxins that affect genomic function of both eukaryotes and prokaryotes. The 375-base pair bacterial gene Streptoalloteichus hindustanus (Sh) ble encodes a small protein, Streptoalloteichus hindustanus bleomycin resistance protein (BRP), that inhibits in vitro DNA cleavage by the prokar...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:The class III antiarrhythmic drugs amiodarone and bretylium tosylate are cationic/amphiphilic, and various substances with these physico-chemical properties are known to directly activate heterotrimeric regulatory G proteins. We asked the question of whether class III antiarrhythmic drugs are also direct G protein act...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:A Walker 256 rat carcinoma cell line (WR) has been shown to be resistant to a broad spectrum of bifunctional nitrogen mustards (NM) in cell culture. The parent cell line (WS) from which the WR cells were selected retains marked sensitivity to this class of drugs. Karyotype analysis showed that the parent WS had a chro...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:Hepatic very-low-density lipoprotein particles (VLDL) containing full-length apolipoprotein B100 are metabolized in the blood stream to low-density lipoprotein (LDL) particles, whose elevated levels increase the risk of atherosclerosis. Statins and bile-acid sequestrants are effective LDL-lowering therapies for many p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.2.269
更新日期：2002-02-01 00:00:00
abstract：:Merbarone (5-[N-phenyl carboxamido]-2-thiobarbituric acid) is an anticancer drug that inhibits the catalytic activity of DNA topoisomerase II (topo II) without damaging DNA or stabilizing DNA-topo II cleavable complexes. Although the cytotoxicity of the complex-stabilizing DNA-topo II inhibitors such as VP-16 (etoposi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-03-01 00:00:00
abstract：:Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24), a member of the IL-10 cytokine gene family, preferentially induces cell death in neoplastic epithelial cells types while sparing their normal counterparts. The effects of mda-7/IL-24 in acute myeloid leukemia (AML) cells have not been extensive...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.068007
更新日期：2010-12-01 00:00:00
abstract：:The D2 dopamine receptor (D2R) was examined for its ability to mediate nuclear factor-kappaB (NF-kappaB) activation through G proteins. Stimulation of D2R-transfected HeLa cells with its agonist quinpirole induced the expression of a NF-kappaB luciferase reporter and formation of NF-kappaB-DNA complex. This response w...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.2.447
更新日期：2003-08-01 00:00:00
abstract：:The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails to bind opioid ligands. We developed two radioligands for the OFQ-R: a tritiated native OFQ peptide ([3H]OFQ) an...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.5.816
更新日期：1997-05-01 00:00:00
abstract：:Electrical recordings were made in Xenopus oocytes to study the modulatory effects of steroids on gamma-aminobutyric acid (GABA) receptors expressed by RNA from mammalian brain and retina. GABA responses expressed by rat cerebral cortex poly(A)+ RNA were bicuculline-sensitive Cl- currents mediated by GABAA receptors. ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:In this work, we evaluate the structural differences of transmembrane helix 3 in rhodopsin and the 5-hydroxytryptamine 1A (5-HT1A) receptor caused by their different amino acid sequence. Molecular dynamics simulations of helix 3 in the 5-HT1A receptor tends to bend toward helix 5, in sharp contrast to helix 3 in rhodo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.15
更新日期：2002-07-01 00:00:00
abstract：:Based on biochemical and ligand binding studies in various tissues and species, evidence for several alpha 2-adrenergic receptor subtypes has accumulated. The current alpha 2-adrenergic receptor classification (alpha 2A, alpha 2B, alpha 2C) is based exclusively on pharmacological criteria. The molecular cloning of thr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Mammalian A2-adenosine receptor binding subunits (A2AR) can be visualized by covalent labeling with the photoaffinity crosslinking ligand 125I-2-[4-[2-[2-[(4-aminophenyl)methylcarbonylamino] ethylaminocarbonyl]ethyl]phenyl]ethylamino-5'-N-ethylcarboxamidoad enosine or directly with the azide derivative described in th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:The co-transfection assay is a novel functional assay using cells transiently transfected with plasmids encoding intracellular receptors and corresponding reporter genes. Using this assay, natural product extracts were tested to identify compounds that modulate intracellular receptor activity, measured as changes in r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:We tested several histamine H(1) receptor (H(1)R) and antagonists for their differences in agonists binding affinities between human and guinea pig H(1)Rs transiently expressed in African green monkey kidney (COS-7) cells. Especially, the bivalent agonist histaprodifen-histamine dimer (HP-HA) shows a higher affinity f...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008847
更新日期：2005-04-01 00:00:00
abstract：:Glucose utilization in isolated islets of Langerhans of the rat was determined by measuring the conversion of [5-3H]glucose (10 mM) to 3H2O. The alpha 2-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the alpha 1-adrenoceptor antagonist prazosin and the beta-adrenoceptor antagonist ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression pattern...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.101808
更新日期：2016-04-01 00:00:00
abstract：:Two structural models have been developed to explain how agonist binding leads to ionotropic glutamate receptor (iGluR) activation. At alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) iGluRs, full and partial agonists close the agonist-binding domain (ABD) to different degrees whereas agonist-induced do...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054254
更新日期：2009-05-01 00:00:00
abstract：:To learn more about the binding conformation of phencyclidine (PCP) and to arrive at analogues of higher affinity, which may serve as noncompetitive N-methyl-D-aspartate receptor antagonists, eight optically pure PCP analogues were designed with the aid of computer. These compounds represent conformationally constrain...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:It has long been believed that the cortical actin cytoskeleton plays an important role in regulating the secretion of hormones and neurotransmitters. In this study, we investigated the control of actin dynamics in primary neuroendocrine cells and determined the relationship of actin dynamics to various components of t...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008474
更新日期：2005-04-01 00:00:00
abstract：:The binding of two anthranilic acid derivatives, glafenic and floctafenic acids, to human erythrocytes and plasma proteins has been investigated in vitro by equilibrium dialysis. Despite their close chemical structures it was shown that the binding of the two compounds to serum albumin, lipoproteins, and erythrocytes ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:Inhibition of cathepsin C, a dipeptidyl peptidase that activates many serine proteases, represents an attractive therapeutic strategy for inflammatory diseases with a high neutrophil burden. We recently showed the feasibility of blocking the activation of neutrophil elastase, cathepsin G, and proteinase-3 with a singl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.045682
更新日期：2008-06-01 00:00:00
abstract：:Effects of ethanol on the function of Ca(2+)-activated Cl- channels activated by G protein-coupled serotonin (5-hydroxytryptamine, (5-HT)1c) and muscarinic M1 cholinergic receptors were studied in Xenopus oocytes expressing mouse whole-brain mRNA. Ethanol (25-200 mM) inhibited currents evoked by both 5-HT and acetylch...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:The interaction of quinidine with a cloned human cardiac potassium channel (HK2) expressed in a stable mouse L cell line was studied using the whole-cell tight-seal voltage-clamp technique. Quinidine (20 microM) did not affect the initial sigmoidal activation time course of the current. However, it reduced the peak cu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:Using [3H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-se...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-02-01 00:00:00
abstract：:The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
