Abstract:
:Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubstituted groups at different key functional locations. The structures revealed that 4 and 2' substituted compounds have more interactions with the protein, cofactor, and solvents when compared with triclosan. New water molecules were found to interact with some of these inhibitors. Substitution at the 2' position of triclosan caused the relocation of a conserved water molecule, leading to an additional hydrogen bond with the inhibitor. This observation can help in conserved water-based inhibitor design. 2' and 4' unsubstituted compounds showed a movement away from the hydrophobic pocket to compensate for the interactions made by the halogen groups of triclosan. This compound also makes additional interactions with the protein and cofactor which compensate for the lost interactions due to the unsubstitution at 2' and 4'. In cell culture, this inhibitor shows less potency, which indicates that the chlorines at 2' and 4' positions increase the ability of the inhibitor to cross multilayered membranes. This knowledge helps us to modify the different functional groups of triclosan to get more potent inhibitors.
journal_name
IUBMB Lifejournal_title
IUBMB lifeauthors
Maity K,Bhargav SP,Sankaran B,Surolia N,Surolia A,Suguna Kdoi
10.1002/iub.327subject
Has Abstractpub_date
2010-06-01 00:00:00pages
467-76issue
6eissn
1521-6543issn
1521-6551journal_volume
62pub_type
杂志文章相关文献
IUBMB LIFE文献大全abstract::Accumulating evidence indicates that there is a critical role of the ubiquitin/proteasome pathway in the regulation of apoptosis. Among the important molecules that couple these two fundamental cellular activities are members of the inhibitor of apoptosis (IAP) protein family. In addition to their well-studied ability...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540500389013
更新日期:2005-12-01 00:00:00
abstract::Synucleinopathies are neurodegenerative diseases characterized by the accumulation of either neuronal/axonal or glial insoluble proteinaceous aggregates mainly composed of α-synuclein (α-syn). Among them, the most common disorders are Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and some fo...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2194
更新日期:2020-04-01 00:00:00
abstract::In Streptomyces fradiae, calcium ions induce alterations in intensity and specificity of the secondary metabolism and stimulate sporulation. Using in vivo labeling, we demonstrate that in S. fradiae phosphorylation of some proteins are also influenced by Ca2+ added exogenously. Calcium ions at physiological concentrat...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/713803699
更新日期:2000-08-01 00:00:00
abstract::In tsRSV-infected NRK (tsNRK) cells, pp60(v-src) reactivation by temperature-shift from a nonpermissive temperature, 39 C, to a permissive one, 32 degrees C, induced the production of inositol phosphates (IPt) and phosphatidylethanol (PEt). This was accompanied by an increase in membrane-associated protein kinase C (P...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/713803467
更新日期:1999-07-01 00:00:00
abstract::Heart disease is the most common cause of morbidity and mortality in Western society and the incidence is projected to increase significantly over the next few decades as our population ages. Heart failure occurs when the heart is unable to pump blood at a rate to commensurate with tissue metabolic requirements and re...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540214312
更新日期:2002-08-01 00:00:00
abstract::A pool of Plasmodium falciparum casein kinase 1 (PfCK1) has been shown to localize to the host red blood cell (RBC) membrane and be secreted to the extracellular medium during trophozoite stage of development. We attempted to identify mechanisms for secretion of PfCK1 and its appearance on the RBC membrane. We found t...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2294
更新日期:2020-06-01 00:00:00
abstract::Cell-surface-bound extracellular DNA (csbDNA) is present on the outer membrane of blood cells, including both red blood cells and leukocytes. Although less well characterized than cell-free DNA (cfDNA) in plasma and serum, leukocyte and red blood cell csbDNA form a considerable fraction of the blood extracellular nucl...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2070
更新日期:2019-09-01 00:00:00
abstract::Depurinating DNA adducts formed by aromatic hydrocarbons and catechol estrogen quinones play a major role in cancer initiation. Most of these adducts depurinate instantaneously, but some guanine adducts depurinate from DNA with half-lives of hours. We report here, that after 10 h at 37 °C, reaction of estradiol-3,4-qu...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.586
更新日期:2012-02-01 00:00:00
abstract::How cells regulate Gq efficacy (initiation and termination of Gq signaling) to effect response remains a central question in pharmacology and drug discovery. Phospholipase C-β1 (PLC-β1) is an effector and a GTPase activating protein (GAP) specific to Gαq. The physiological function of PLC-β1 GAP remains unclear and co...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1218
更新日期:2013-11-01 00:00:00
abstract::Ovarian cancer (OC) is one of the most lethal gynaecological cancers, which usually has a poor prognosis due to late diagnosis. A large percentage of the OC cell population is in a nonproliferating and quiescent stage, which poses a barrier to success when using most chemotherapeutic agents. Recent studies have shown ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1035
更新日期:2012-07-01 00:00:00
abstract::Cooperative effects in ligand binding and dissociation kinetics are much less investigated than steady state kinetics or equilibrium binding. Nevertheless, cooperativity in ligand binding leads necessarily to characteristic properties with respect to kinetic properties of the system. In case of positive cooperativity ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.459
更新日期:2011-05-01 00:00:00
abstract::Advanced glycation end-products comprise a complex and heterogeneous group of compounds that have been implicated in diabetes-related complications. The importance of the Maillard reaction is depicted by the formation of reactive intermediate products known as α-oxoaldehydes, such as 3-deoxyglucosone (3-DG). This prod...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1318
更新日期:2014-10-01 00:00:00
abstract::Members of the GATA family of transcription factors play key roles in the differentiation of specific cell lineages by regulating the expression of target genes. Three GATA factors play distinct roles in hematopoietic differentiation. In order to better understand how these GATA factors function to regulate genes thro...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2195
更新日期:2020-01-01 00:00:00
abstract::Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor survival outcomes that is relatively resistant to chemotherapy. N6-Methyladenosine (m6A) modification, the most prevalent modification of eukaryotic messenger RNA, is involved in the progression of various tumors. However, it is un...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2410
更新日期:2020-11-17 00:00:00
abstract::The pathogenetic mechanism of the most extensively investigated A3243G mutated tRNALeu(UUR) gene, which causes the MELAS encephalomyopathy, maternally inherited diabetes, or chronic progressive external ophlthalmoplegia, is still unresolved, despite the numerous investigations on the topic. Previous evidences presente...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/1521654031000110190
更新日期:2003-03-01 00:00:00
abstract::Anthracyclines are a class of antitumor drugs widely used for the treatment of a variety of malignancy, including leukemias, lymphomas, sarcomas, and carcinomas. Different mechanisms have been proposed for anthracycline antitumor effects including free-radical generation, DNA intercalation/binding, activation of signa...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540252774829
更新日期:2001-07-01 00:00:00
abstract::Heparin and its various derivatives affect cancer progression in humans. In this study, we show that heparin uptaken intracellularly by melanoma cells activated a signaling cascade, which in turn inhibited melanoma cell adhesion and migration. The reduced ability of M5 cells to adhere onto the fibronectin (FN) substra...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.421
更新日期:2011-02-01 00:00:00
abstract::The members of the GATA family of transcription factors have homologous zinc fingers and bind to similar sequence motifs. Recent advances in genome-wide technologies and the integration of bioinformatics data have led to a better understanding of how GATA factors regulate gene expression; GATA-factor-induced transcrip...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2169
更新日期:2020-01-01 00:00:00
abstract::Uncoupling proteins (UCPs) are regulated H+ transporters and a subfamily of the mitochondrial carrier family. Whereas UCP1 in brown adipose tissue has a well-defined role in thermogenesis, the roles of other UCPs are still tentative, such as in control of immune response, oxygen radical formation, and insulin secretio...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540152845975
更新日期:2001-09-01 00:00:00
abstract::Worldwide, one of the most prevalent forms of chronic disease is alcoholic fatty liver, which may progress to more severe forms of liver injury including steatohepatitis, fibrosis, and cirrhosis. The molecular mechanisms by which ethanol consumption causes accumulation of hepatic lipid are multiple and complex. Chroni...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.124
更新日期:2008-12-01 00:00:00
abstract::Combining two analytical techniques, HPLC and liquid secondary ion mass spectrometry, the orientation of liposomal membrane-bound melittin was analyzed through its trypsin-digested products. We found that trypsin can access all proteolytic sites of the membrane-bound melittin when the liposomes have no transmembrane p...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/152165400300001543
更新日期:2000-09-01 00:00:00
abstract::The pathophysiology of some inflammatory arterial diseases (such as vasculitis, atherogenesis and aneurysms) has been widely investigated in the last decades. Among different soluble molecules, proinflammatory cytokines (such as TNF-α, IL-1 and IL-6) were shown to trigger critical pathways regulating these arterial di...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.1344
更新日期:2015-01-01 00:00:00
abstract::Crude brazilin extract from Sappan wood has demonstrated strong anti tumor activity in the mouse model of human bladder carcinoma and clinical trial for intravesical therapy. Purified brazilin was confirmed the most active molecule in inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and viab...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1357
更新日期:2015-03-01 00:00:00
abstract::Arginine biosynthesis pathway is crucial to the survival and pathogenesis of Mycobacterium tuberculosis (Mtb). Arginine is a critical amino acid that contributes to the inflection of cellular immune responses during pathogenesis. Argininosuccinate lyase from Mtb (MtArgH), the last enzyme in the pathway, catalyzes the ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1683
更新日期:2017-11-01 00:00:00
abstract::Elevated homocysteine levels are known to be a risk factor for congenital cardiac septal defects (CCSDs), but the mechanism underlying this effect is unknown. The genetic variants that were significantly associated with circulating homocysteine concentrations have been systematically identified through the genome-wide...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1651
更新日期:2017-09-01 00:00:00
abstract::Calcineurin (CN) is the only serine/threonine specific protein phosphatase regulated by Ca(2+) /calmodulin (CaM), which is composed of catalytic A subunit (CNA) and regulatory B subunit (CNB). Tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) is an essential component in the Toll like receptors and TNF ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1060
更新日期:2012-09-01 00:00:00
abstract::Cardiac hypoxia plays a significant role in various types of heart disease, and improper treatment of hypoxia often leads to myocardial cell damage or even death. Transcriptome profiling and open chromatin mapping have been used as powerful tools to understand the development of heart disease, but the interplay betwee...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2297
更新日期:2020-08-01 00:00:00
abstract::In this article, the experiments used to construct the ambient pH-signaling network involved in the secretion of enzymes by filamentous fungi have been reviewed, focusing on the phosphate-repressible phosphatases in Aspergillus nidulans. Classic and molecular genetics have been used to demonstrate that proteolysis of ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1217
更新日期:2013-11-01 00:00:00
abstract::Hepatitis C virus (HCV) is an enveloped positive-strand RNA virus of the Flaviviridae family. It has a genome of about 9,600 nucleotides encoding a large polyprotein (about 3,000 amino acids) that is processed by cellular and viral proteases into at least 10 structural and nonstructural viral proteins. A novel HCV pro...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.201
更新日期:2009-07-01 00:00:00
abstract::Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to ...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/1521654031000153012
更新日期:2003-06-01 00:00:00