Abstract:
:The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by a FAD-dependent UDP-Galp mutase. When the enzyme is reduced by sodium dithionite, its catalytic efficiency increases significantly. Since the overall transformation exhibits no net change in the redox state of the parties involved, how the enzyme-bound FAD plays an active role in the reaction mechanism is puzzling. In this paper, we report our study of the catalytic properties of UDP-Galp mutase reconstituted with deaza-FADs. It was found that the mutase reconstituted with FAD or 1-deazaFAD has comparable activity, while that reconstituted with 5-deazaFAD is catalytically inactive. Because 5-deazaFAD is restricted to net two-electron process, yet FAD and 1-deazaFAD can undergo concerted two-electron as well as stepwise one-electron redox reactions, the above results support a radical mechanism for the mutase catalyzed reaction. In addition, the activity of the mutase reconstituted with FAD was found to increase considerably at high pHs. These observations have allowed us to propose a new mechanism involving one-electron transfer from the reduced FAD to an oxocarbenium intermediate generated by C-1 elimination of UDP to give a hexose radical and a flavin semiquinone. Subsequent radical recombination leads to a coenzyme-substrate adduct which may play a central role to facilitate the opening and recyclization of the galactose ring. A deprotonation step, accompanied or followed the electron transfer step, to increase the nucleophilicity of the flavin radical anion may account for the activity enhancement at pH > 8.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Huang Z,Zhang Q,Liu HWdoi
10.1016/j.bioorg.2003.08.002subject
Has Abstractpub_date
2003-12-01 00:00:00pages
494-502issue
6eissn
0045-2068issn
1090-2120pii
S0045206803001044journal_volume
31pub_type
杂志文章abstract::Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic interven...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2015.06.004
更新日期:2015-08-01 00:00:00
abstract::The inhibition of viral targets might provide new therapies for coronavirus disease abbreviated as COVID-19. The rational drug design identified as much of the recent discoveries of potent drugs molecule against any targets. This results in an improvement in bindings for better potency and selectivity. The drugs conta...
journal_title:Bioorganic chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bioorg.2020.104027
更新日期:2020-08-01 00:00:00
abstract::The ethanolic extract obtained from the stems of Glycosmis pentaphylla was found to suppress antigen-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. Four new geranylated 2-quinolone alkaloids, named glycopentanolones A-D (1-4), and 12 known metabolites (5-16) were isolated from the ethanolic extract...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.03.069
更新日期:2019-06-01 00:00:00
abstract::Hydrogen sulfide (H2S) is a biologically important gaseous molecule that exhibits promising protective effects against a variety of pathological processes. For example, it was recognized as a blood pressure lowering agent. Aligned with the need for easily modifiable platforms for the H2S supply, we report here the pre...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.102941
更新日期:2019-07-01 00:00:00
abstract::Crataegus pinnatifida has been famous for its nutritional purpose. However, systematic investigation on the bioactive constituents is still lacking, although this fruit has been reported for its cytotoxic effect before. In this study, two pairs of new lignan enantiomers (1a/1b, 2a/2b), which isolated using chiral chro...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104267
更新日期:2020-11-01 00:00:00
abstract::The overexpression of P-glycoprotein plays an important role in the process of multidrug resistance (MDR). P-gp inhibitors are one of the effective strategies to reverse tumor MDR. Novel P-gp inhibitors with phthalazinone scaffolds were designed, synthesized and evaluated. Compound 26 was found to be the most promisin...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.01.039
更新日期:2019-05-01 00:00:00
abstract::Glycosphingolipids (GSLs) have been implicated as playing major roles in cellular interactions and control of cell proliferation in muticellular organisms. Moreover GSLs and other sphingolipids such as sphingomyelins, ceramides and sphingosines serve a variety of roles in signal transduction. Hence, identification of ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2007.10.002
更新日期:2008-04-01 00:00:00
abstract::Chemical investigation of the roots of Croton crassifolius led to the isolation of five pyran-2-one derivatives, including two brand new compounds (1-2), one new natural product (3) and two known compounds (4-5). Their structures and absolute configurations were established by spectroscopic analyses as well as compari...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.05.020
更新日期:2018-09-01 00:00:00
abstract::A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) elect...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.03.051
更新日期:2019-06-01 00:00:00
abstract::Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase responsible for development of various tumor types. Aiming to explore new potent inhibitors, two series of 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized on the base of structure-based design strategy....
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104092
更新日期:2020-09-01 00:00:00
abstract::To discover new natural-product-based pesticides, we structurally modified andrographolide, a labdane diterpenoid isolated from Andrographis paniculata, and stereoselectively prepared a series of 12α-(substituted)benzylamino-14-deoxyandrographolide derivatives (I-V). Three-dimensional structures of compounds 3c, 3d, I...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.01.020
更新日期:2019-05-01 00:00:00
abstract::Herein, substituted imidazole-pyrazole hybrids (2a-2n) were prepared via a multi component reaction employing pyrazole-4-carbaldehydes (1a-1d), ammonium acetate, benzil and arylamines as reactants. All the new compounds were characterized through their spectral and elemental analyses. Further these compounds were test...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.10.047
更新日期:2019-02-01 00:00:00
abstract::The fungus Mucor circinelloides exhibits high potential for green chemistry and technological applications. Recently M. circinelloides, which so far was considered mainly as a platform for biodiesel production, was found to exhibit high ene-reductase activity. In our current research we applied this promising microorg...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103548
更新日期:2020-03-01 00:00:00
abstract::Epichlorohydrin (a probable human carcinogen) was allowed to react with adenosine and the adducts were characterized by NMR and UV spectroscopy, and mass spectrometry. The adduct initially formed was 1-(3-chloro-2-hydroxypropyl)-adenosine, which subsequently ring closures to 1,N(6)-(2-hydroxypropyl)-adenosine at neutr...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2006.01.005
更新日期:2006-06-01 00:00:00
abstract::The development of vasorelaxant as the antihypertensive drug is important as it produces a rapid and direct relaxation effect on the blood vessel muscles. Resveratrol (RV), as the most widely studied stilbenoid and the lead compound, inducing the excellent vasorelaxation effect through the multiple signalling pathways...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104239
更新日期:2020-11-01 00:00:00
abstract::This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2015.08.006
更新日期:2015-12-01 00:00:00
abstract::This study deals with synthesis of a new set of benzofuran and 5H-furo[3,2-g]chromone linked various heterocyclic functionalities using concise synthetic approaches aiming to gain new antiproliferative candidates against MCF-7 breast cancer cells of p38α MAP kinase inhibiting activity. The biological data proved the s...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2017.12.029
更新日期:2018-02-01 00:00:00
abstract::Cyclooxygenase-2 is one of the prominent enzymes to cause an increased production of prostaglandins during inflammation and immune responses. Cyclooxygenase-2 expression is up-regulated in inflammatory conditions owing to the induction by different inflammatory stimuli including cytokines, and therefore, the expressio...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104140
更新日期:2020-10-01 00:00:00
abstract::A new series of triazolopyrimidines and thiazolopyrimidine hydrobromides was designed and prepared as topoisomerase II inhibitors. Screening of all synthesized compounds was carried out by the National Cancer Institute (NCI) of USA. Activity against 60 human cancer cell lines representing different cancer types was de...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104134
更新日期:2020-10-01 00:00:00
abstract::The structure-function relation of YR-10 (YGKPVAVPAR) was investigated by synthesizing four structural analogs of that including YHR-10 (YGKHVAVHAR), GA-8 (GKPVAVPA), GHA-8 (GKHVAVHA), and PAR-3 (PAR). GA-8 (GKPVAVPA) was synthesized on the basis of simulated enzymatic gastrointestinal digestion performed by bioinform...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.03.057
更新日期:2019-06-01 00:00:00
abstract::The severe acute respiratory syndrome (SARS) virus depends on a chymotrypsin-like cysteine proteinase (3CL(pro)) to process the translated polyproteins to functional viral proteins. This enzyme is a target for the design of potential anti-SARS drugs. A series of ketones and corresponding mono- and di-fluoro ketones ha...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2008.01.001
更新日期:2008-10-01 00:00:00
abstract::BRAF mutation is commonly known in a number of human cancer types. It is counted as a potential component in treating cancer. In this study, based on structural optimization of previously reported inhibitors (3-fluro substituted derivatives of imidazo[2,1-b]thiazole-based scaffold), we designed and synthesized sixteen...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103967
更新日期:2020-07-01 00:00:00
abstract::We reported an useful protocol for the labeling of the second domain of the Vascular Endothelial Growth Factor Receptor 1 (VEGFR1D2), a small protein ligand able to bind VEGF, the main regulator of angiogenesis. We developed a bioconjugation strategy based on the use of oxime-ligation reaction conjugating an aldehyde ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103160
更新日期:2019-10-01 00:00:00
abstract::Galactokinase catalyses the phosphorylation of galactose at the expense of ATP. Like other members of the GHMP family of kinases it is postulated to function through an active site base mechanism in which Asp-186 abstracts a proton from galactose. This asparate residue was altered to alanine and to asparagine by site-...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2011.03.001
更新日期:2011-06-01 00:00:00
abstract::Inhibition of soluble epoxide hydrolase (sEH) is considered as a promising target to reduce blood pressure, improve insulin sensitivity, and decrease inflammation. In this study, a series of some novel quinazoline-4(3H)-one derivatives (3a-t) with varying steric and electronic properties was designed, synthesized and ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103736
更新日期:2020-06-01 00:00:00
abstract::In an aim at developing new antiproliferative agents, new series of benzothiazole/benzoxazole and/or benzimidazole substituted pyrazole derivatives 11a-c, 12a-c and 13a-c were prepared and evaluated for their antiproliferative activity against breast carcinoma (MCF-7) and non-small cell lung cancer (A549) cell lines. ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2017.07.007
更新日期:2017-10-01 00:00:00
abstract::Novel benzothiazole-based compounds were designed and synthesized as potential antimicrobial agents with dual DNA gyrase/topoisomerase IV inhibitory activity. The structures of the newly synthesized compounds were established on the basis of spectral (IR, NMR, MS) and elemental analyses. Most of the studied compounds ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103437
更新日期:2020-01-01 00:00:00
abstract::Autophagy is an intracellular degradation/recycling pathway that provides nutrients and building blocks to cellular metabolism and keeps the cytoplasm clear of obsolete proteins and organelles. During recent years, dysregulated autophagy activity has been reported to be a characteristic of many different disease types...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.03.021
更新日期:2019-06-01 00:00:00
abstract::BRAFV600E mutation has been detected in various malignant tumours. Developing of potent BRAFV600E inhibitors is considered a leading step in the way to cure different cancer types. In the current work, a series of 38 4-(1H-imidazol-5-yl)pyridin-2-amine derivatives was designed and synthesized using Dabrafenib as a lea...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104508
更新日期:2021-01-01 00:00:00
abstract::Inhibition of carbonic anhydrases (CAs, EC 4.2.1.1) has clinical importance for the treatment of several diseases. They participate in crucial regulatory mechanisms for balancing intracellular and extracellular pH of the cells. Among CA isoforms, selective inhibition of hCA IX has been linked to decreasing of cell gro...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103222
更新日期:2019-11-01 00:00:00