Abstract:
:Eicosanoids are potent lipid mediators involved in central physiological processes such as hemostasis, renal function and parturition. When formed in excess, eicosanoids become critical players in a range of pathological conditions, in particular pain, fever, arthritis, asthma, cardiovascular disease and cancer. Eicosanoids are generated via oxidative metabolism of arachidonic acid along the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Specific lipid species are formed downstream of COX and LOX by specialized synthases, some of which reside on the nuclear and endoplasmic reticulum, including mPGES-1, FLAP, LTC4 synthase, and MGST2. These integral membrane proteins are members of the family "membrane-associated proteins in eicosanoid and glutathione metabolism" (MAPEG). Here we focus on this enzyme family, which encompasses six human members typically catalyzing glutathione dependent transformations of lipophilic substrates. Enzymes of this family have evolved to combat the topographical challenge and unfavorable energetics of bringing together two chemically different substrates, from cytosol and lipid bilayer, for catalysis within a membrane environment. Thus, structural understanding of these enzymes are of utmost importance to unravel their molecular mechanisms, mode of substrate entry and product release, in order to facilitate novel drug design against severe human diseases.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Thulasingam M,Haeggström JZdoi
10.1016/j.jmb.2020.07.020subject
Has Abstractpub_date
2020-08-21 00:00:00pages
4999-5022issue
18eissn
0022-2836issn
1089-8638pii
S0022-2836(20)30475-7journal_volume
432pub_type
杂志文章,评审abstract::Mammalian alphaB-crystallin is highly expressed both in lens epithelium and lens fibers. In contrast, gammaF-crystallin is highly expressed in the lens fiber cells. Crystallin gene expression in lens is regulated at the level of transcription by a sparse number of specific DNA-binding transcription factors. Here, we r...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.07.102
更新日期:2004-11-19 00:00:00
abstract::We describe a new method for local protein structure prediction based on a library of short sequence pattern that correlate strongly with protein three-dimensional structural elements. The library was generated using an automated method for finding correlations between protein sequence and local structure, and contain...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1943
更新日期:1998-08-21 00:00:00
abstract::Normal type I collagen is a heterotrimer of two alpha1(I) and one alpha2(I) chains, but various genetic and environmental factors result in synthesis of homotrimers that consist of three alpha1(I) chains. The homotrimers completely replace the heterotrimers only in rare recessive disorders. In the general population, ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.08.008
更新日期:2008-10-31 00:00:00
abstract::The single mutation L30 K in the Hu-Yap65 WW domain increased the stability of the complex with the peptide GTPPPPYTVG (K(d)=40(+/-5) microM). Here we report the refined solution structure of this complex by NMR spectroscopy and further derived structure-activity relationships by using ligand peptide libraries with tr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.5199
更新日期:2001-12-14 00:00:00
abstract::Structural properties and folding of interleukin-1 receptor antagonist (IL-1ra), a therapeutically important cytokine with a symmetric beta-trefoil topology, are characterized using optical spectroscopy, high-resolution NMR, and size-exclusion chromatography. Spectral contributions of two tryptophan residues, Trp17 an...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.02.031
更新日期:2007-05-11 00:00:00
abstract::3-Methylitaconate-Delta-isomerase (Mii) participates in the nicotinate fermentation pathway of the anaerobic soil bacterium Eubacterium barkeri (order Clostridiales) by catalyzing the reversible conversion of (R)-3-methylitaconate (2-methylene-3-methylsuccinate) to 2,3-dimethylmaleate. The enzyme is also able to catal...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.06.052
更新日期:2009-08-21 00:00:00
abstract::The beta-globin gene cluster of human, gorilla and chimpanzee contain the same number and organization of beta-type globin genes: 5'-epsilon (embryonic)-G gamma and A gamma (fetal)-psi beta (inactive)-delta and beta (adult)-3'. We have isolated the psi beta-globin gene regions from the three species and determined the...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(84)90256-0
更新日期:1984-12-25 00:00:00
abstract::Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.08.063
更新日期:2006-10-20 00:00:00
abstract::Transverse sections (100 to 140 nm thick) of the flight muscles of the fleshfly Phormia terrae-novae and the housefly Musca domestica were studied. The images of 56 tubular myosin filaments of the fleshfly and 62 filaments of the housefly were digitized and computer processed by rotational averaging. The rotational po...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(88)90637-7
更新日期:1988-06-05 00:00:00
abstract::The nucleotide sequences of nine genes corresponding to tRNA(Ser)4 or tRNA(Ser)7 of Drosophila melanogaster were determined. Eight of the genes compose the major tRNA(Ser)4,7 cluster at 12DE on the X chromosome, while the other is from 23E on the left arm of chromosome 2. Among the eight X-linked genes, five different...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(87)90553-5
更新日期:1987-10-05 00:00:00
abstract::Cytosolic heat shock protein 90 (Hsp90) has been shown to be essential for many infectious pathogens and is considered a potential target for drug development. In this study, we have carried out biochemical characterization of Hsp90 from a poorly studied protozoan parasite of clinical importance, Entamoeba histolytica...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.01.008
更新日期:2014-04-17 00:00:00
abstract::Protein tyrosine phosphatase PTPN13, also known as PTP-BL in mice, represents a large multi-domain non-transmembrane scaffolding protein that contains five consecutive PDZ domains. Here, we report the solution structures of the extended murine PTPN13 PDZ3 domain in its apo form and in complex with its physiological li...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2018.08.023
更新日期:2018-10-19 00:00:00
abstract::Single crystals of the soluble glucose dehydrogenase (GDH) from Acinetobacter calcoaceticus have been grown by the vapour diffusion method. These crystals diffract to beyond 2.1 A and are suitable for X-ray crystallography. The space group was determined to be P2(1) with unit cell parameters a = 55.5 A, b = 104.5 A, c...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1553
更新日期:1993-10-20 00:00:00
abstract::l-Rhamnose is a 6-deoxyhexose that is found in a variety of different glycoconjugates in the cell walls of pathogenic bacteria. The precursor of l-rhamnose is dTDP-l-rhamnose, which is synthesised from glucose- 1-phosphate and deoxythymidine triphosphate (dTTP) via a pathway requiring four enzymes. Significantly this ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.4470
更新日期:2001-03-16 00:00:00
abstract::An essential consequence of growth factor-mediated signal transduction is the generation of intracellular H(2)O(2). It operates as a second messenger in the control of actin microfilament dynamics, causing rapid and dramatic changes in the morphology and motile activity of stimulated cells. Little is understood about ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.04.056
更新日期:2007-07-06 00:00:00
abstract::alpha-Chemokines comprise a family of cytokines that are chemotactic for neutrophils and have a structure similar to platelet factor 4 (PF4), in which the first two cysteine residues are separated by one residue (Cys-X-Cys). The two alpha-chemokines, connective tissue activating peptide-III (CTAP-III) and neutrophil a...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0796
更新日期:1997-02-21 00:00:00
abstract::The folding of multidomain proteins often proceeds in a hierarchical fashion with individual domains folding independent of one another. A large single-domain protein, however, can consist of multiple modules whose folding may be autonomous or interdependent in ways that are unclear. We used coarse-grained simulations...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.07.007
更新日期:2008-10-03 00:00:00
abstract::Fumarase C purified from Escherichia coli has been crystallized in the presence of polyethylene glycol in both a citrate buffer at pH 5.3 and a 3-(4-morpholino)-propanesulfonic acid buffer at pH 7.5 yielding two crystal forms. An orthorhombic C222(1) form was obtained in citrate at pH 5.3 and an orthorhombic I222 form...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1264
更新日期:1993-05-05 00:00:00
abstract::Ricin is a potent cytotoxin which has been used widely in the construction of therapeutic agents such as immunotoxins. Recently it has been used by governments and underground groups as a poison. There is interest in identifying and designing effective inhibitors of the ricin A chain (RTA). In this study computer-assi...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0865
更新日期:1997-03-14 00:00:00
abstract::Pex19p, a primarily cytosolic protein, is essential for the biogenesis of numerous peroxisomal membrane proteins (PMPs); however, its precise function is unclear. Pex19p might function as a PMP-specific chaperone, a cycling PMP-receptor protein, a PMP membrane insertion factor, or an association/dissociation factor of...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.01.013
更新日期:2005-03-11 00:00:00
abstract::At high concentrations, type I pN-collagen, pC-collagen and procollagen (the first 2 generated from procollagen by enzymic cleavage of C-propeptides and N-propeptides, respectively) can all be made to assemble in vitro into thin D-periodic sheets or tapes. Scanning transmission electron microscopy mass measurements sh...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(91)90385-j
更新日期:1991-07-05 00:00:00
abstract::Here, we report the molecular characterization of the human cytomegalovirus uracil DNA glycosylase (UNG) UL114. Purified UL114 was shown to be a DNA glycosylase, which removes uracil from double-stranded and single-stranded DNA. However, kinetic analysis has shown that viral UNG removed uracil more slowly compared wit...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.05.028
更新日期:2008-08-29 00:00:00
abstract::The powerful explanatory paradigm of molecular biology requiring form to co-evolve with function has again been proven successful when, over the recent two decades, a wealth of biological functions have been uncovered for RNA. Previously considered as a mere mediator of the genetic code, RNA is now acknowledged as a k...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1006/jmbi.1999.3312
更新日期:1999-12-10 00:00:00
abstract::Missense mutations of the p53 tumour suppressor gene induce the formation of proteins with an altered affinity for DNA. These mutant proteins have either a wild-type or a mutant conformation. It has been established that, on association with wild-type protein, molecules with mutant conformation can drive the wild-type...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1897
更新日期:1998-08-14 00:00:00
abstract::This study describes an algorithm that finds rho-independent transcription terminators in bacterial genomes and evaluates the accuracy of its predictions. The algorithm identifies terminators by searching for a common mRNA motif: a hairpin structure followed by a short uracil-rich region. For each terminator, an energ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.3836
更新日期:2000-08-04 00:00:00
abstract::Plasmodium knowlesi parasites isolated from a rhesus monkey vaccinated with a 143,000/140,000 Mr merozoite surface protein no longer expressed this protein. To study the molecular basis for the mutations, a lambda gt11 cDNA expression library constructed from the original parasite clone was screened with rabbit antise...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(88)90204-5
更新日期:1988-10-05 00:00:00
abstract::S100A4 (metastasin) is a member of the S100 family of calcium-binding proteins that is directly involved in tumorigenesis. Until recently, the only structural information available was the solution NMR structure of the inactive calcium-free form of the protein. Here we report the crystal structure of human S100A4 in t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.04.076
更新日期:2008-10-31 00:00:00
abstract::Elastomeric proteins are molecular springs found not only in a variety of biological machines and tissues, but also in biomaterials of superb mechanical properties. Regulating the mechanical stability of elastomeric proteins is not only important for a range of biological processes, but also critical for the use of en...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.03.046
更新日期:2008-05-16 00:00:00
abstract::S100P is a small calcium-binding protein of the S100 EF-hand-containing family of proteins. Elevated levels of its mRNA are reported to be associated with the progression to hormone independence and metastasis of prostate cancer and to be associated with loss of senescence in human breast epithelial cells in vitro. Th...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(02)01278-0
更新日期:2003-01-24 00:00:00
abstract::Avidin, a basic tetrameric glycoprotein, isolated from hen egg-white, binds up to four molecules of biotin with exceptionally high affinity. The presence of tryptophanyl residues in the active site pointed out the opportunity of correlating the protein fluorescence with biotin binding. We have performed both steady st...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1600
更新日期:1994-09-30 00:00:00