Comparative sequence analysis in the sialyltransferase protein family: analysis of motifs.

Abstract:

:The sialyltransferase family represents a group of enzymes that transfers sialic acid from its common nucleotide sugar donor, CMP-NeuAc, to the terminal carbohydrates group of various glycoproteins and glycolipids. Cloning of these enzymes from mammalian sources indicated these are all type II membrane proteins with topological features common to other glycosyltransferases. To date, 20 cloned enzymes with distinct substrate specificity have been obtained for mammalian sialyltransferases. These account for four subfamilies according to the carbohydrate linkages synthesized, namely, ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia. Comparative peptide sequence analysis of these cloned enzymes showed the presence of four conserve sialylmotifs, namely 'L'- (for long), 'S'- (for short), -'III' (for being third position in sequence) and '-VS' (for very small), common to all of this protein family. Experiments by site-directed mutagenesis showed evidence that these motifs contribute to the binding of either donor or the acceptor or both. While the L-sialylmotif contributes to the binding of the donor substrate, the motifs -III and -VS contribute to the binding of the acceptor substrate. S-sialymotif, on the other hand, contributes to the binding of both the donor and acceptor substrates. Apparently, a disulfide linkage between the L-sialylmotif and the S-sialylmotif bringing all of these motifs closer together facilitates such interaction with the substrates. In addition, although with no experimental evidence, comparative sequence analysis also suggests a strong correlation of linkage specificity of these enzymes with the peptide sequence closer to these sialylmotifs.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Datta AK

doi

10.2174/138945009788488422

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

483-98

issue

6

eissn

1389-4501

issn

1873-5592

journal_volume

10

pub_type

杂志文章,评审
  • Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation.

    abstract::Human proteins are subjected to more than 200 known post-translational modifications (PTMs) (e.g., phosphorylation, glycosylation, ubiquitination, S-nitrosylation, methylation, Nacetylation, and citrullination) and these PTMs can alter protein structure and function with consequent effects on the multitude of pathways...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150202160954

    authors: Witalison EE,Thompson PR,Hofseth LJ

    更新日期:2015-01-01 00:00:00

  • Kidney diseases and chemokines.

    abstract::Infiltrating inflammatory cells into the kidney mediate the initiation and progression of damage by direct cytotoxicity, the secretion of soluble factors such as cytokines and proteases, or by the subsequent induction of further immune response. Before leukocytes can exert their effects on renal damage or repair, they...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006775270213

    authors: Panzer U,Steinmetz OM,Stahl RA,Wolf G

    更新日期:2006-01-01 00:00:00

  • Key targets and relevant inhibitors for the drug discovery of tuberculosis.

    abstract::Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis), killing about two million people worldwide each year. An increase in the prevalence of drug-resistant strains of M. tuberculosis in the past decades has renewed focus on the development of new drugs that can...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450111314060009

    authors: Xiong X,Xu Z,Yang Z,Liu Y,Wang D,Dong M,Parker EJ,Zhu W

    更新日期:2013-06-01 00:00:00

  • Insights into the Targeting Potential of Thymoquinone for Therapeutic Intervention Against Triple-negative Breast Cancer.

    abstract:BACKGROUND:Thymoquinone (TQ) is a bioactive phytoconstituent obtained from Nigella sativa (black seeds). It has promising potential in cancer prevention. OBJECTIVE:Previous studies have shown that TQ can modulate signaling pathways responsible for cancer progression, thus enhancing the efficacy and improving the safet...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450118666170612095959

    authors: Barkat MA,Harshita,Ahmad J,Khan MA,Beg S,Ahmad FJ

    更新日期:2018-01-01 00:00:00

  • Targeting JAK3 and BTK tyrosine kinases with rationally-designed inhibitors.

    abstract::Multifunctional rational drug design of protein tyrosine kinases inhibitors allows a potent drug to be utilized to treat more than one disease for greater patient benefits. Many protein tyrosine kinases (PTK), including Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), have been identified as potential drug ta...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006776054997

    authors: Vassilev AO,Tibbles HE,DuMez D,Venkatachalam TK,Uckun FM

    更新日期:2006-03-01 00:00:00

  • Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences.

    abstract:BACKGROUND:Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of cl...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945009788982513

    authors: Dauri M,Faria S,Gatti A,Celidonio L,Carpenedo R,Sabato AF

    更新日期:2009-08-01 00:00:00

  • HIV-1 Tat-Mediated Calcium Dysregulation and Neuronal Dysfunction in Vulnerable Brain Regions.

    abstract::Despite the success of combined antiretroviral therapy, more than half of HIV-1-infected patients in the USA show HIV-associated neurological and neuropsychiatric deficits. This is accompanied by anatomical and functional alterations in vulnerable brain regions of the mesocorticolimbic and nigrostriatal systems that r...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150531162212

    authors: Hu XT

    更新日期:2016-01-01 00:00:00

  • Is surfactant a promising additive drug in ALI/ARDS-patients?

    abstract::The rationale for surfactant replacement therapy in patients with acute respiratory distress syndrome (ARDS) is to restore the normal composition of the surfactant system, as well as to overcome ongoing inactivation of present surfactant. Indeed, surfactant replacement therapy can normalize the composition of the surf...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450043345399

    authors: Schultz MJ,Kesecioglu J

    更新日期:2004-07-01 00:00:00

  • Osteoarthritis: aging of matrix and cells--going for a remedy.

    abstract::It has been known for a very long time that aging is the most prominent risk factor for the initiation and progression of osteoarthritis. This might be related to continuous mechanical wear and tear and/or result from time/age-related modifications of cartilage matrix components. Also a mere loss of viable cells over ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945007779940070

    authors: Aigner T,Haag J,Martin J,Buckwalter J

    更新日期:2007-02-01 00:00:00

  • Oxidative stress: meeting multiple targets in pathogenesis of diabetic nephropathy.

    abstract::Excessive production of reactive oxygen species is an important mechanism underlying the pathogenesis of diabetes associated macrovascular and microvascular complications including diabetic nephropathy. Diabetic nephropathy is characterized by glomerular enlargement, early albuminuria and progressive glomerulosclerosi...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450115666140321120635

    authors: Arora MK,Singh UK

    更新日期:2014-05-01 00:00:00

  • Catalytic DNA: a novel tool for gene suppression.

    abstract::RNA, as an intermediate in the production of every gene encoded protein and the genetic material of many pathogenic viruses, presents an attractive target for both biological and therapeutic manipulation. Despite its extensive involvement in living systems, its chemical diversity based on four units is relatively low ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450023347722

    authors: Cairns MJ,Saravolac EG,Sun LQ

    更新日期:2002-06-01 00:00:00

  • Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review.

    abstract::Phytometabolites are functional elements derived from plants and most of them exhibit therapeutic characteristics such as anti-cancer, anti-inflammatory and anti-oxidant effects. Phytometabolites exert their anti-cancer effect by targeting multiple signaling pathways. One of the remarkable phenomena targeted by phytom...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450117666160401124842

    authors: Hasanpourghadi M,Looi CY,Pandurangan AK,Sethi G,Wong WF,Mustafa MR

    更新日期:2017-01-01 00:00:00

  • Vascular disrupting agents (VDA) in oncology: advancing towards new therapeutic paradigms in the clinic.

    abstract::Vascular Disrupting Agents (VDA) are a potential new class of oncology drugs that have garnered attention recently as a number of these agents have entered into Phase 2-3 studies. Currently available data suggest how the subsequent evolution of these agents into clinical practice may proceed, with new therapeutic para...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945011798829366

    authors: Spear MA,LoRusso P,Mita A,Mita M

    更新日期:2011-12-01 00:00:00

  • Modulation of GABA(A) receptors by natural products and the development of novel synthetic ligands for the benzodiazepine binding site.

    abstract::Nature provides science and society with a virtually unlimited supply of structurally diverse and biologically active molecules; the natural products. While some are directly useful in commercial applications, others are valuable for studying and understanding biological phenomena at the molecular level. An example is...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945011798109509

    authors: Nilsson J,Sterner O

    更新日期:2011-10-01 00:00:00

  • Update on statins: hope for osteoporotic fracture healing treatment.

    abstract::Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmeno...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/13894501113149990195

    authors: Ibrahim N',Mohamed N,Shuid AN

    更新日期:2013-12-01 00:00:00

  • Amendatory Effect of Flavonoids in Alzheimer's Disease Against Mitochondrial Dysfuntion.

    abstract::Flavonoids are chromene analogues abundantly found in plants. It is always of curiosity to discover natural flavonoid structures, since living things, including human, are routinely exposed to these compounds through many dietaries. Indeed, numerous studies conducted so far on flavonoids to display their diverse biolo...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450122666210120144921

    authors: Gulcan HO,Orhan IE

    更新日期:2021-01-20 00:00:00

  • Diacylglycerol kinases as emerging potential drug targets for a variety of diseases.

    abstract::Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating (consuming) DAG to yield PA. Ten mammalian DGK isozymes have been identified to date. In addition to two or three cysteine-rich C1 domains (protein kinase C-like zinc finger stru...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945008785132394

    authors: Sakane F,Imai S,Kai M,Yasuda S,Kanoh H

    更新日期:2008-08-01 00:00:00

  • Epigenetic Therapies and Potential Drugs for Treating Human Cancer.

    abstract::Epigenetic modifications ensure the maintenance of normal cellular functions, and their dysregulation is frequently found in many disease states, including cancer. Nowadays, the most studied epigenetic dysregulation associated with tumorigenesis, cancer progression and metastasis refers to the variations in DNA methyl...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450121666200325093104

    authors: Lin SQ,Li X

    更新日期:2020-01-01 00:00:00

  • Targeting PPAR isoforms following CNS injury.

    abstract::A major focus has developed for the discovery of proregenerative and neuroprotective therapeutic agents to help the millions of Americans who receive a CNS injury annually. Tribulations have been encountered along the way due to the complicated set of pathways that are initiated post-injury. To target this complicated...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450111314070003

    authors: Yonutas HM,Sullivan PG

    更新日期:2013-06-01 00:00:00

  • Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role in COVID-19 Immunopathology.

    abstract:BACKGROUND:The Coronavirus Disease 2019 (COVID-19) is becoming the major health issue in recent human history with thousands of deaths and millions of cases worldwide. Newer research and old experience with other corona-viruses highlighted a probable underlying mechanism of disturbance of the renin-angiotensin system (...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450121666201020154033

    authors: Vieira C,Nery L,Martins L,Jabour L,Dias R,Simões E Silva AC

    更新日期:2020-10-20 00:00:00

  • Cellular and Molecular Networks in Chronic Myeloid Leukemia: The Leukemic Stem, Progenitor and Stromal Cell Interplay.

    abstract::The use of imatinib, second and third generation ABL tyrosine kinase inhibitors (TKI) (i.e. dasatinib, nilotinib, bosutinib and ponatinib) made CML a clinically manageable and, in a small percentage of cases, a cured disease. TKI therapy also turned CML blastic transformation into a rare event; however, disease progre...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450117666160615074120

    authors: Perrotti D,Silvestri G,Stramucci L,Yu J,Trotta R

    更新日期:2017-01-01 00:00:00

  • C. elegans: an all in one model for antimicrobial drug discovery.

    abstract::One approach to identify new drugs with antimicrobial activities is to screen large libraries of molecules directly for their capacity to block the growth of bacterial or fungal monocultures. A more relevant way to assess both a product's efficacy and its potential cytotoxicity is undoubtedly to use an in vivo infecti...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945011795677854

    authors: Squiban B,Kurz CL

    更新日期:2011-06-01 00:00:00

  • Mucosal healing in ulcerative colitis: where do we stand?

    abstract::Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation affecting the colonic mucosa, that can extend to the whole large bowel. The severity of mucosal lesions directly reflects the disease activity and severity and may be prognostic for an aggressive behavior of the pathol...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945011796818216

    authors: Fiorino G,Cesarini M,Indriolo A,Malesci A

    更新日期:2011-09-01 00:00:00

  • Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma.

    abstract::Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without che...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450121666200719011234

    authors: Cheng L,Li N,Xu XL,Mao WM

    更新日期:2020-01-01 00:00:00

  • Expression and functions of galectin-1 in sensory and motoneurons.

    abstract::Galectin-1 (Gal1) was the first identified member of the galectin family of beta-galactosidase-binding proteins. Gal1 has important roles in processes fundamental to growth and survival of an organism, including cell adhesion, cell proliferation and apoptosis, and is expressed in many tissues, including the nervous sy...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450054021864

    authors: Gaudet AD,Steeves JD,Tetzlaff W,Ramer MS

    更新日期:2005-06-01 00:00:00

  • Human Immunodeficiency Virus-1 Cell-To-Cell Transmission And Antiviral Strategies: An Overview.

    abstract::HIV-1 replicates by infecting new target cells either as cell-free viral particle or, much more efficiently, via cell-to-cell viral transmission. Cell-mediated viral spread, in which the infected cell directly transfers the viral particles to target cells via cell-cell contacts, in vitro is up to three orders of magni...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:

    authors: Casartelli N

    更新日期:2015-08-25 00:00:00

  • Drug Development Strategy for Type 2 Diabetes: Targeting Positive Energy Balances.

    abstract::Newer classes of medications have been proven useful in glycemic control in type 2 diabetes (T2D), but many do not appear capable to slow down the progressive loss of ß-cell function, or to improve population-level glycemic control. Positive energy balance, e.g. surplus energy intake over expenditure, is at the core f...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450120666181217111500

    authors: Liu Z,Yang B

    更新日期:2019-01-01 00:00:00

  • The functions and structure of ABC transporters: implications for the design of new inhibitors of Pgp and MRP1 to control multidrug resistance (MDR).

    abstract::Multidrug resistance (MDR) is a kind of acquired resistance of microorganisms and cancer cells to chemotherapic drugs that are characterized by different chemical structure and different mechanism of action. Classic MDR is the consequence of the over-expression of a variety of proteins that extrude the chemotherapic f...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006777709520

    authors: Teodori E,Dei S,Martelli C,Scapecchi S,Gualtieri F

    更新日期:2006-07-01 00:00:00

  • Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms: preclinical and clinical implications.

    abstract::Cell proliferation, differentiation, and survival are regulated by a number of extracellular hormones, growth factors, and cytokines in complex organisms. The transduction of the signals by these factors from the outside to the nucleus often requires the presence of small intracellular proteins (i.e. ras and other sma...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450053765833

    authors: Caraglia M,Budillon A,Tagliaferri P,Marra M,Abbruzzese A,Caponigro F

    更新日期:2005-05-01 00:00:00

  • α7 nicotinic acetylcholine receptor mediated neuroprotection in Parkinson's disease.

    abstract::Parkinson's disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine recep...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945012800399026

    authors: Kawamata J,Suzuki S,Shimohama S

    更新日期:2012-05-01 00:00:00