The molecular structure of the μ‎-opioid receptor

2018 ◽  
Author(s):  
Roger D. Knaggs
Keyword(s):  
Crystal Structure ◽  
Side Effects ◽  
Opioid Receptor ◽  
Three Dimensional ◽  
Binding Pocket ◽  
Dimensional Structure ◽  
Ligand Interaction ◽  
Analgesic Effects ◽  
Interaction Sites ◽  
Potential Ligand

The landmark paper discussed in this chapter describes the crystal structure of the μ‎-opioid receptor (also known as MOP-1). Opioids are some of the oldest known drugs and have been used for over 4,000 years; however, in addition to having beneficial analgesic effects, they are associated with a myriad of side effects that can minimize their use. Although the gene sequences of the opioid receptors were determined in the 1990s it has taken much longer to translate this into visualizing their three-dimensional structure. The μ‎-opioid receptor consists of seven transmembrane α‎-helices that are connected by three extracellular loops and three intracellular loops, with a wide open binding pocket which offers many potential ligand interaction sites, and evidence of dimerization. Understanding the crystal structure of the μ‎-opioid receptor in much more detail aids explanation of the molecular determinants of ligand recognition and selectivity and will be of use in designing novel opioids with improved efficacy and fewer side effects.

The first crystal structure of the peptidase domain of the U32 peptidase family

2015 ◽  
Vol 71 (12) ◽  
pp. 2505-2512 ◽  
Author(s):  
Magdalena Schacherl ◽  
Angelika A. M. Montada ◽  
Elena Brunstein ◽  
Ulrich Baumann
Keyword(s):  
Crystal Structure ◽  
Catalytic Mechanism ◽  
Quaternary Structure ◽  
Catalytic Domain ◽  
Three Dimensional ◽  
Zinc Ion ◽  
Crystal Structure Analysis ◽  
Dimensional Structure ◽  
Sequence Motifs ◽  
Conserved Sequence

The U32 family is a collection of over 2500 annotated peptidases in the MEROPS database with unknown catalytic mechanism. They mainly occur in bacteria and archaea, but a few representatives have also been identified in eukarya. Many of the U32 members have been linked to pathogenicity, such as proteins fromHelicobacterandSalmonella. The first crystal structure analysis of a U32 catalytic domain fromMethanopyrus kandleri(genemk0906) reveals a modified (βα)8TIM-barrel fold with some unique features. The connecting segment between strands β7 and β8 is extended and helix α7 is located on top of the C-terminal end of the barrel body. The protein exhibits a dimeric quaternary structure in which a zinc ion is symmetrically bound by histidine and cysteine side chains from both monomers. These residues reside in conserved sequence motifs. No typical proteolytic motifs are discernible in the three-dimensional structure, and biochemical assays failed to demonstrate proteolytic activity. A tunnel in which an acetate ion is bound is located in the C-terminal part of the β-barrel. Two hydrophobic grooves lead to a tunnel at the C-terminal end of the barrel in which an acetate ion is bound. One of the grooves binds to aStrep-Tag II of another dimer in the crystal lattice. Thus, these grooves may be binding sites for hydrophobic peptides or other ligands.

A new three-dimensional anionic cadmium(II) dicyanamide network

2014 ◽  
Vol 70 (11) ◽  
pp. 1054-1056 ◽  
Author(s):  
Qiang Li ◽  
Hui-Ting Wang
Keyword(s):  
Crystal Structure ◽  
Aqueous Solution ◽  
Unit Cell Volume ◽  
Three Dimensional ◽  
Building Blocks ◽  
The Other ◽  
Dimensional Structure ◽  
Cadmium Nitrate ◽  
Nitrate Tetrahydrate ◽  
Anionic Framework

A new cadmium dicyanamide complex, poly[tetramethylphosphonium [μ-chlorido-di-μ-dicyanamido-κ4N1:N5-cadmium(II)]], [(CH3)4P][Cd(NCNCN)2Cl], was synthesized by the reaction of tetramethylphosphonium chloride, cadmium nitrate tetrahydrate and sodium dicyanamide in aqueous solution. In the crystal structure, each CdIIatom is octahedrally coordinated by four terminal N atoms from four anionic dicyanamide (dca) ligands and by two chloride ligands. The dicyanamide ligands play two different roles in the building up of the structure; one role results in the formation of [Cd(dca)Cl]2building blocks, while the other links the building blocks into a three-dimensional structure. The anionic framework exhibits a solvent-accessible void of 673.8 Å3, amounting to 47.44% of the total unit-cell volume. The cavities in the network are occupied by pairs of tetramethylphosphonium cations.

scholarly journals Crystal structure of 2-benzylamino-4-(4-methoxyphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile

2014 ◽  
Vol 70 (12) ◽  
pp. 525-527 ◽  
Author(s):  
R. A. Nagalakshmi ◽  
J. Suresh ◽  
S. Maharani ◽  
R. Ranjith Kumar ◽  
P. L. Nilantha Lakshman
Keyword(s):  
Crystal Structure ◽  
Pyridine Ring ◽  
Three Dimensional ◽  
Chair Conformation ◽  
Dimensional Structure ◽  
Compound C ◽  
Centroid Distance ◽  
Steric Crowding ◽  
Benzene Rings ◽  
Group A

The title compound, C25H25N3O, comprises a 2-aminopyridine ring fused with a cycloheptane ring, which adopts a chair conformation. The central pyridine ring (r.m.s. deviation = 0.013 Å) carries three substituents,viz.a benzylamino group, a methoxyphenyl ring and a carbonitrile group. The N atom of the carbonitrile group is significantly displaced [by 0.2247 (1) Å] from the plane of the pyridine ring, probably due to steric crowding involving the adjacent substituents. The phenyl and benzene rings are inclined to one another by 58.91 (7)° and to the pyridine ring by 76.68 (7) and 49.80 (6)°, respectively. In the crystal, inversion dimers linked by pairs of N—H...Nnitrilehydrogen bonds generateR22(14) loops. The dimers are linked by C—H...π and slipped parallel π–π interactions [centroid–centroid distance = 3.6532 (3) Å] into a three-dimensional structure.

scholarly journals Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

2013 ◽  
Vol 288 (23) ◽  
pp. 16460-16475 ◽  
Author(s):  
Linda J. Olson ◽  
Ramiro Orsi ◽  
Solana G. Alculumbre ◽  
Francis C. Peterson ◽  
Ivan D. Stigliano ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Three Dimensional ◽  
Binding Pocket ◽  
Dimensional Structure ◽  
Mannose Residue ◽  
Glucosidase Ii ◽  
Mannose 6 Phosphate ◽  
First Time ◽  
Conserved Residue

Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.

scholarly journals Crystal structure of a tankyrase 1–telomere repeat factor 1 complex

2016 ◽  
Vol 72 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Bo Li ◽  
Ruihong Qiao ◽  
Zhizhi Wang ◽  
Weihong Zhou ◽  
Xin Li ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Large Scale ◽  
Sparse Matrix ◽  
Critical Role ◽  
Three Dimensional ◽  
Mitotic Cell ◽  
Ankyrin Repeat ◽  
Dimensional Structure ◽  
Telomere Repeat ◽  
Tankyrase 1

Telomere repeat factor 1 (TRF1) is a subunit of shelterin (also known as the telosome) and plays a critical role in inhibiting telomere elongation by telomerase. Tankyrase 1 (TNKS1) is a poly(ADP-ribose) polymerase that regulates the activity of TRF1 through poly(ADP-ribosyl)ation (PARylation). PARylation of TRF1 by TNKS1 leads to the release of TRF1 from telomeres and allows telomerase to access telomeres. The interaction between TRF1 and TNKS1 is thus important for telomere stability and the mitotic cell cycle. Here, the crystal structure of a complex between the N-terminal acidic domain of TRF1 (residues 1–55) and a fragment of TNKS1 covering the second and third ankyrin-repeat clusters (ARC2-3) is presented at 2.2 Å resolution. The TNKS1–TRF1 complex crystals were optimized using an `oriented rescreening' strategy, in which the initial crystallization condition was used as a guide for a second round of large-scale sparse-matrix screening. This crystallographic and biochemical analysis provides a better understanding of the TRF1–TNKS1 interaction and the three-dimensional structure of the ankyrin-repeat domain of TNKS.

scholarly journals Crystal structure of 3-deoxy-3-nitromethyl-1,2;5,6-di-O-isopropylidene-α-D-allofuranose

2016 ◽  
Vol 72 (3) ◽  
pp. 314-317
Author(s):  
Jevgeņija Lugiņina ◽  
Vitālijs Rjabovs ◽  
Dmitrijs Stepanovs
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Title Compound ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Compound C

The title compound, C13H21NO7{systematic name: (3aR,5S,6R,6aR)-5-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-6-(nitromethyl)tetrahydrofuro[2,3-d][1,3]dioxole}, consists of a substituted 2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxolane skeleton. The furanose ringAadopts aoT4conformation. The fused dioxolane ringBand the substituent dioxolane ringCalso have twisted conformations. There are no strong hydrogen bonds in the crystal structure: only weak C—H...O contacts are present, which link the molecules to form a three-dimensional structure.

scholarly journals Synthesis and crystal structure of a new polymorph of potassium europium(III) bis(sulfate) monohydrate, KEu(SO4)2·H2O

2018 ◽  
Vol 74 (2) ◽  
pp. 242-245 ◽  
Author(s):  
Avijit Kumar Paul
Keyword(s):  
Crystal Structure ◽  
Topological Analysis ◽  
Structural Connectivity ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Monoclinic Space Group ◽  
Hydrothermal Conditions ◽  
Metal Sulfate ◽  
Synthesis And Crystal Structure ◽  
Trigonal Prismatic

The mixed-metal sulfate, KEu(SO4)2·H2O, has been obtained as a new polymorph using hydrothermal conditions. The crystal structure is isotypic with NaCe(SO4)2·H2O and shows a three-dimensional connectivity of the tetrahedral sulfate units with EuIII and KI ions. Tricapped trigonal–prismatic EuO9 units and square-antiprismatic KO8 units link the SO4 tetrahedra, building the three-dimensional structure. Topological analysis reveals the existence of two nodes with 6- and 10-connected nets. The compound was previously reported [Kazmierczak & Höppe (2010). J. Solid State Chem. 183, 2087–2094] in the monoclinic space group P21/c with a similar structural connectivity and coordination environments to the present compound.

scholarly journals Crystal structure of trichlorido(4′-ferrocenyl-2,2′:6′,2′′-terpyridine-κ3N,N′,N′′)iridium(III) acetonitrile disolvate

2015 ◽  
Vol 71 (3) ◽  
pp. m69-m70 ◽  
Author(s):  
Bambar Davaasuren ◽  
Harihara Padhy ◽  
Alexander Rothenberger
Keyword(s):  
Crystal Structure ◽  
Title Compound ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Ferrocenyl Group ◽  
Distorted Octahedral ◽  
Chloride Ligands ◽  
Solvent Molecules

In the title compound, [FeIr(C5H5)(C20H14N3)Cl3]·2CH3CN, the central IrIIIatom is sixfold coordinated by three chloride ligands and three terpyridine N atoms in a slightly distorted octahedral fashion. The terpyridine ligand is functionalized at the 4′-position with a ferrocenyl group, the latter being in an eclipsed conformation. In the crystal, molecules are stacked in rows parallel to [001], with the acetonitrile solvent molecules situated between the rows. An extensive network of intra- and intermolecular C—H...Cl interactions is present, stabilizing the three-dimensional structure.

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