Abstract：
:The cyclooxygenases (COX-1 and COX-2) catalyze the rate-limiting step in the biosynthesis of prostaglandins, and are the pharmacological targets of non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors (coxibs). Ibuprofen (IBP) is one of the most commonly available over-the-counter pharmaceuticals in the world. The anti-inflammatory and analgesic properties of IBP are thought to arise from inhibition of COX-2 rather than COX-1. While an X-ray crystal structure of IBP bound to COX-1 has been solved, no such structure exists for the cognate isoform COX-2. We have determined the crystal structure of muCOX-2 with a racemic mixture of (R/S)-IBP. Our structure reveals that only the S-isomer of IBP was bound, indicating that the S-isomer possesses higher affinity for COX-2 than the R-isomer. Mutational analysis of Arg-120 and Tyr-355 at the entrance of the cyclooxygenase channel confirmed their role in binding and inhibition of COX-2 by IBP. Our results provide the first atomic level detail of the interaction between IBP and COX-2.
journal_name
J Struct Bioljournal_title
Journal of structural biologyauthors
Orlando BJ,Lucido MJ,Malkowski MGdoi
10.1016/j.jsb.2014.11.005subject
Has Abstractpub_date
2015-01-01 00:00:00pages
62-6issue
1eissn
1047-8477issn
1095-8657pii
S1047-8477(14)00243-3journal_volume
189pub_type
杂志文章abstract：:Centrioles are microtubule-based structures that play essential roles in cell division and cilia biogenesis. Cep120 is an important protein for correct centriole formation and mutations in the Cep120 gene cause severe human diseases like Joubert syndrome and complex ciliopathies. Here, we show that Cep120 contains thr...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2018.01.009
更新日期：2018-07-01 00:00:00
abstract：:Although the fundamental steps in Fourier-based image analysis of electron micrographs of helical structures have not changed significantly since the techniques were developed 30 years ago, there have been developments which aid both the analysis itself and the interpretation of results. Increases in computational res...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.1996.0027
更新日期：1996-01-01 00:00:00
abstract：:Long-depth imaging of specific gene expression in the midgestation whole-mount mouse embryo (WME) is demonstrated with single-photon excitation (1PE) confocal fluorescence microscopy and fluorescence in situ hybridization. Expression domains of Pax-6 mRNA transcripts were labeled with an in situ hybridization probe th...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.2000.4238
更新日期：2000-07-01 00:00:00
abstract：:Titin is a giant elastic protein responsible for passive force generated by the stretched striated-muscle sarcomere. Passive force develops in titin's extensible region which consists of the PEVK segment in series with tandemly arranged immunoglobulin (Ig)-like domains. Here we studied the mechanics of tandem Ig segme...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.2002.4458
更新日期：2002-01-01 00:00:00
abstract：:The emergence of electron tomography as a tool for three dimensional structure determination of cells and tissues has brought its own challenges for the preparation of thick sections. High pressure freezing in combination with freeze substitution provides the best method for obtaining the largest volume of well-preser...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2007.09.002
更新日期：2008-03-01 00:00:00
abstract：:Integration of fluorescence light and transmission electron microscopy into the same device would represent an important advance in correlative microscopy, which traditionally involves two separate microscopes for imaging. To achieve such integration, the primary technical challenge that must be solved regards how to ...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2013.10.018
更新日期：2014-01-01 00:00:00
abstract：:Members of the Ku superfamily are DNA-end-binding proteins involved in non-homologous end-joining (NHEJ) DNA repair. The published crystal structure of human Ku-DNA complex reveals a heterodimer that forms a ring around dsDNA by means of the Ku core modules. These modules contain a highly conserved seven-stranded β-ba...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2010.05.011
更新日期：2010-12-01 00:00:00
abstract：:Structures of biological macromolecules determined by transmission cryoelectron microscopy (cryo-TEM) and three-dimensional image reconstruction are often displayed as surface-shaded representations with depth cueing along the viewed direction (Z cueing). Depth cueing to indicate distance from the center of virus part...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.1997.3902
更新日期：1997-10-01 00:00:00
abstract：:Infection of plants by Zucchini Yellow Mosaic Virus (ZYMV) induces severe ultrastructural changes. The aim of this study was to investigate ultrastructural changes during ZYMV-infection in Cucurbita pepo L. plants on the two and three dimensional (2D and 3D) level and to correlate these changes with the spread of ZYMV...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2014.03.006
更新日期：2014-05-01 00:00:00
abstract：:Calnexin is a molecular chaperone that facilitates folding of glycoproteins in the endoplasmic reticulum (ER). The cloned lumenal domain of canine calnexin, cnxDeltaTMC, retains its biological activity without the transmembrane and cytosolic region. For the purpose of structure determination we generated a crystalliza...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.1998.4032
更新日期：1998-11-01 00:00:00
abstract：:Methods predicting protein secondary structure improved substantially in the 1990s through the use of evolutionary information taken from the divergence of proteins in the same structural family. Recently, the evolutionary information resulting from improved searches and larger databases has again boosted prediction a...
journal_title：Journal of structural biology
pub_type： 杂志文章,评审
doi：10.1006/jsbi.2001.4336
更新日期：2001-05-01 00:00:00
abstract：:The Caliciviridae is a family of nonenveloped, icosahedral, positive-sense single-stranded RNA viruses. This family of viruses consists of both animal and human pathogens. Adapting human caliciviruses to cell culture has not been successful, whereas some animal caliciviruses, including San Miguel sea lion virus, have ...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/s1047-8477(02)00583-x
更新日期：2003-02-01 00:00:00
abstract：:3,4-dihydroxy 2-butanone 4-phosphate synthase (DHBPS) and GTP cyclohydrolase-II (GTPCH-II) are the two initial enzymes involved in riboflavin biosynthesis pathway, which has been shown to be essential for the pathogens. In Mycobacterium tuberculosis (Mtb), the ribA2 gene (Rv1415) encodes for the bi-functional enzyme w...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2011.01.013
更新日期：2011-05-01 00:00:00
abstract：:Commonly employed data models for maximum likelihood refinement of electron microscopy images behave poorly in the presence of normalization errors. Small variations in background mean or signal brightness are relatively common in cryo-electron microscopy data, and varying signal-to-noise ratios or artifacts in the im...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2009.02.007
更新日期：2009-05-01 00:00:00
abstract：:The AAA+ family of proteins play fundamental roles in all three kingdoms of life. It is thought that they act as molecular chaperones in aiding the assembly or disassembly of proteins or protein complexes. Recent structural studies on a number of AAA+ family proteins have revealed that they share similar structural el...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2003.11.022
更新日期：2004-04-01 00:00:00
abstract：:Three-dimensional crystals were obtained for the membrane domain of the human erythrocyte anion exchanger (AE1, Band 3). Protein homogeneity and stability and the delicate balance between the detergent used and the amount of phospholipids copurifying are critical to the formation of three-dimensional crystals of the A...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/s1047-8477(02)00010-2
更新日期：2002-03-01 00:00:00
abstract：:The mechanisms which cause macromolecules to form discrete compartments within the nucleus are not understood. Here, two ubiquitous compartments, nucleoli, and PML bodies, are shown to disassemble when K562 cell nuclei expand in medium of low monovalent cation concentration; their major proteins dispersed as seen by i...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2003.12.008
更新日期：2004-06-01 00:00:00
abstract：:Microcrystals of the chlorophyll binding protein, CP43, isolated from spinach thylakoid membranes have been studied by electron microscopy both in negative stain and in vitreous ice. Image analyses of three characteristic views show that the crystals are built of five different layers perpendicular to the c-axis. Each...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.2000.4294
更新日期：2000-09-01 00:00:00
abstract：:Integral membrane proteins are involved in virtually every cellular process. Precisely regulating these machineries would allow controlling many human and vertebrate diseases. Embedded into cellular membranes, membrane proteins establish molecular interactions that sensitively react to environmental changes and to mol...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2007.02.010
更新日期：2007-08-01 00:00:00
abstract：:Overproduction and crystallization of Bacillus stearothermophilus ribosomal protein S7 (BstS7), a primary 16S rRNA binding protein and also a translational repressor protein, have been performed to analyze its three-dimensional structure by X-ray crystallography. Ribosomal protein BstS7 was expressed in the cytoplasmi...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.1997.3907
更新日期：1997-10-01 00:00:00
abstract：:Nacre is the iridescent inner lining of many mollusk shells, with a unique lamellar structure at the sub-micron scale, and remarkable resistance to fracture. Despite extensive studies, nacre formation mechanisms remain incompletely understood. Here we present 20-nm, 2°-resolution polarization-dependent imaging contras...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2013.10.002
更新日期：2013-12-01 00:00:00
abstract：:Proteins isolated from marine invertebrates are frequently characterized by exceptional structural and functional properties. ShPI-1, a BPTI Kunitz-type inhibitor from the Caribbean Sea anemone Stichodactyla helianthus, displays activity not only against serine-, but also against cysteine-, and aspartate proteases. As...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2012.08.009
更新日期：2012-11-01 00:00:00
abstract：:Sub-nanometer resolution structure determination is becoming a common practice in electron cryomicroscopy of macromolecular assemblies. The data for these studies have until now been collected on photographic film. Using cytoplasmic polyhedrosis virus (CPV), a previously determined structure, as a test specimen, we sh...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2004.02.004
更新日期：2004-08-01 00:00:00
abstract：:Titin is a giant protein responsible for passive-tension generation in muscle sarcomeres. Here, we used single-molecule AFM force spectroscopy to investigate the mechanical characteristics of a recombinant construct from the human cardiac-specific N2B-region, which harbors a 572-residue unique sequence flanked by two ...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2006.02.017
更新日期：2006-08-01 00:00:00
abstract：:A characteristic feature of the dense phases formed by fiber-shaped molecules is their organization into parallel rods packed in a hexagonal or pseudo-hexagonal lateral network. This is typically the case for the collagen triple helices inside fibrils, as confirmed by recent X-ray diffraction experiments carried out o...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2010.11.018
更新日期：2011-02-01 00:00:00
abstract：:Three questions central to understanding the initiation of DNA replication in eukaryotes are: (1) Does DNA synthesis begin at a defined place? (2) What determines replication initiation sites? (3) What regulates an origin to fire only once per cell cycle? A key player in this is the origin recognition complex (ORC), r...
journal_title：Journal of structural biology
pub_type： 杂志文章,评审
doi：10.1016/s1047-8477(02)00538-5
更新日期：2002-10-01 00:00:00
abstract：:In this paper, we seek to provide an introduction to the fast-moving field of digital video on the Internet, from the viewpoint of the biological microscopist who might wish to store or access videos, for instance in image databases such as the BioImage Database (http://www.bioimage.org). We describe and evaluate the ...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1006/jsbi.1999.4097
更新日期：1999-04-01 00:00:00
abstract：:Crustaceans form clots by the rapid crosslinking of a hemolymph clottable protein (CP) to form long, branched polymers. Clotting limits hemolymph loss from wounds as well as playing a part in the innate immune response. CP is a 420 kDa homodimer with a large quantity of associated lipid, primarily the carotenoid pigme...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2005.06.008
更新日期：2005-09-01 00:00:00
abstract：:The crystal structure of the YckF protein from Bacillus subtilis was determined with MAD phasing and refined at 1.95A resolution. YckF forms a tight tetramer both in crystals and in solution. Conservation of such oligomerization in other phosphate sugar isomerases indicates that the crystallographically observed tetra...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2004.04.006
更新日期：2004-10-01 00:00:00
abstract：:Polynoid worm elytra emit light when mechanically or electrically stimulated. Specialized cells, the photocytes, contain light emitting machineries, the photosomes. Successive stimulations induce light intensity variations and show a coupling within and between photosomes. Here, we describe, using electron tomography ...
journal_title：Journal of structural biology
pub_type： 杂志文章
doi：10.1016/j.jsb.2017.12.001
更新日期：2018-04-01 00:00:00
