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https://www.readbyqxmd.com/read/28329765/structural-insights-into-adiponectin-receptors-suggest-ceramidase-activity
#1
Ieva Vasiliauskaité-Brooks, Remy Sounier, Pascal Rochaix, Gaëtan Bellot, Mathieu Fortier, François Hoh, Luigi De Colibus, Chérine Bechara, Essa M Saied, Christoph Arenz, Cédric Leyrat, Sébastien Granier
Adiponectin receptors (ADIPORs) are integral membrane proteins that control glucose and lipid metabolism by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of ceramide to produce sphingosine and a free fatty acid (FFA). The crystal structures of the two receptor subtypes, ADIPOR1 and ADIPOR2, show a similar overall seven-transmembrane-domain architecture with large unoccupied cavities and a zinc binding site within the seven transmembrane domain. However, the molecular mechanisms by which ADIPORs function are not known...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28322963/the-effect-of-oxaloacetic-acid-on-tyrosinase-activity-and-structure-integration-of-inhibition-kinetics-with-docking-simulation
#2
Lin Gou, Jinhyuk Lee, Hao Hao, Yong-Doo Park, Yi Zhan, Zhi-Rong Lü
Oxaloacetic acid (OA) is naturally found in organisms and well known as an intermediate of citric acid cycle producing ATP. We evaluated the effects of OA on tyrosinase activity and structure via integrating methods of enzyme kinetics and computational simulations. OA was found to be a reversible inhibitor of tyrosinase and its induced mechanism was the parabolic non-competitive inhibition type (IC50=17.5±0.5mM and Ki=6.03±1.36mM). Kinetic measurements by real-time interval assay showed that OA induced multi-phasic inactivation process composing with fast (k1) and slow (k2) phases...
March 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28322781/characterization-of-akr1b16-a-novel-mouse-aldo-keto-reductase
#3
Joan Giménez-Dejoz, Susanne Weber, Oleg A Barski, Gabriele Möller, Jerzy Adamski, Xavier Parés, Sergio Porté, Jaume Farrés
Aldo-keto reductases (AKRs) are distributed in three families and multiple subfamilies in mammals. The mouse Akr1b3 gene is clearly orthologous to human AKR1B1, both coding for aldose reductase, and their gene products show similar tissue distribution, regulation by osmotic stress and kinetic properties. In contrast, no unambiguous orthologs of human AKR1B10 and AKR1B15.1 have been identified in rodents. Although two more AKRs, AKR1B7 and AKR1B8, have been identified and characterized in mouse, none of them seems to exhibit properties similar to the human AKRs...
March 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28320963/conformational-dynamics-and-role-of-the-acidic-pocket-in-asic-ph-dependent-gating
#4
Sabrina Vullo, Gaetano Bonifacio, Sophie Roy, Niklaus Johner, Simon Bernèche, Stephan Kellenberger
Acid-sensing ion channels (ASICs) are proton-activated Na(+) channels expressed in the nervous system, where they are involved in learning, fear behaviors, neurodegeneration, and pain sensation. In this work, we study the role in pH sensing of two regions of the ectodomain enriched in acidic residues: the acidic pocket, which faces the outside of the protein and is the binding site of several animal toxins, and the palm, a central channel domain. Using voltage clamp fluorometry, we find that the acidic pocket undergoes conformational changes during both activation and desensitization...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28319389/potential-antiosteoporotic-natural-product-lead-compounds-that-inhibit-17%C3%AE-hydroxysteroid-dehydrogenase-type-2
#5
Anna Vuorinen, Roger T Engeli, Susanne Leugger, Fabio Bachmann, Muhammad Akram, Atanas G Atanasov, Birgit Waltenberger, Veronika Temml, Hermann Stuppner, Liselotte Krenn, Sylvin B Ateba, Dieudonné Njamen, Rohan A Davis, Alex Odermatt, Daniela Schuster
17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts the active steroid hormones estradiol, testosterone, and 5α-dihydrotestosterone into their weakly active forms estrone, Δ(4)-androstene-3,17-dione, and 5α-androstane-3,17-dione, respectively, thereby regulating cell- and tissue-specific steroid action. As reduced levels of active steroids are associated with compromised bone health and onset of osteoporosis, 17β-HSD2 is considered a target for antiosteoporotic treatment. In this study, a pharmacophore model based on 17β-HSD2 inhibitors was applied to a virtual screening of various databases containing natural products in order to discover new lead structures from nature...
March 20, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28316096/biochemical-characterization-and-structural-insight-into-aliphatic-%C3%AE-amino-acid-adenylation-enzymes-idnl1-and-cmis6
#6
Jolanta Cieślak, Akimasa Miyanaga, Ryoma Takaku, Makoto Takaishi, Keita Amagai, Fumitaka Kudo, Tadashi Eguchi
Macrolactam antibiotics such as incednine and cremimycin possess an aliphatic β-amino acid as a starter unit of their polyketide chain. In the biosynthesis of incednine and cremimycin, unique stand-alone adenylation enzymes IdnL1 and CmiS6 select and activate the proper aliphatic β-amino acid as a starter unit. In this study, we describe the enzymatic characterization and the structural basis of substrate specificity of IdnL1 and CmiS6. Functional analysis revealed that IdnL1 and CmiS6 recognize 3-aminobutanoic acid and 3-aminononanoic acid, respectively...
March 18, 2017: Proteins
https://www.readbyqxmd.com/read/28315686/crystal-structure-of-the-catalytic-domain-of-clostridium-perfringens-neuraminidase-in-complex-with-a-non-carbohydrate-based-inhibitor-2-cyclohexylamino-ethanesulfonic-acid
#7
Youngjin Lee, Hyung-Seop Youn, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Jung Youn Kang, Young Bae Ryu, Mi Sun Jin, Ki Hun Park, Soo Hyun Eom
Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302935/factor-x-deficiency-with-heterozygous-mutations-of-novel-p-g435s-and-known-p-g244r-in-a-patient-presenting-with-severe-umbilical-hemorrhage
#8
Yoko Matsuo, Tatsuki Mizuochi, Miho Mitsuo, Shinichiro Nakagawa, Shuichi Ozono, Koichiro Ueda, Yoko Sogabe, Ritsuko Seki, Kenji Soejima, Takashi Okamura, Yushiro Yamashita
A 10-day-old male patient was referred to our hospital with severe umbilical bleeding. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prominently prolonged. Plasma coagulation factor X (FX) activity and antigen levels were 1% and 0.6%, respectively. A DNA sequence analysis of his leukocytes revealed a compound heterozygous state; known Gly244 to Arg (p.G244R) in exon 6 and a novel mutation of Gly 435 to Ser (p.G435S) in exon 8. A pedigree analysis showed that p.G244R originated from the paternal side, while p...
March 15, 2017: Kurume Medical Journal
https://www.readbyqxmd.com/read/28298817/comparative-evaluation-of-coenzyme-q10-based-gel-and-0-8-hyaluronic-acid-gel-in-treatment-of-chronic-periodontitis
#9
Varun Sharma, Rajan Gupta, Parveen Dahiya, Mukesh Kumar
BACKGROUND: The anti-inflammatory and immune enhancing effects of coenzyme Q10 (CoQ10) and hyaluronic acid are well established in medical literature. The present study was undertaken to evaluate their role in chronic periodontitis. MATERIALS AND METHODS: One hundred twenty sites in 24 patients with clinically confirmed periodontitis were included in the study. A split-mouth design was used for intrasulcular application of CoQ10 as adjunct to scaling and root planing (SRP), 0...
July 2016: Journal of Indian Society of Periodontology
https://www.readbyqxmd.com/read/28292631/probing-the-activity-of-nthl1-orthologs-by-targeting-conserved-amino-acid-residues
#10
Susan M Robey-Bond, Meredith A Benson, Ramiro Barrantes-Reynolds, Jeffrey P Bond, Susan S Wallace
The base excision repair DNA glycosylases, EcoNth and hNTHL1, are homologous, with reported overlapping yet different substrate specificities. The catalytic amino acid residues are known and are identical between the two enzymes although the exact structures of the substrate binding pockets remain to be determined. We sought to explore the sequence basis of substrate differences using a phylogeny-based design of site-directed mutations. Mutations were made for each enzyme in the vicinity of the active site and we examined these variants for glycosylase and lyase activity...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28291685/synthesis-and-molecular-docking-studies-of-new-furochromone-derivatives-as-p38%C3%AE-mapk-inhibitors-targeting-human-breast-cancer-mcf-7-cells
#11
Kamelia M Amin, Yasmin M Syam, Manal M Anwar, Hamed I Ali, Tamer M Abdel-Ghani, Aya M Serry
Based on the reported high expression of p38α MAP kinase in invasive breast cancers and the activity of different functionalized chromone derivatives as p38α inhibitors, a new set of 4,9-dimethoxy/4-methoxy-7-methyl-5-oxo-5H-furo[3,2-g]chromone derivatives were efficiently synthesized aiming to introduce new p38α MAP kinase suppressors as new anti-breast cancer tools. Using GOLD program, molecular docking study of the target compounds into p38α MAP kinase binding pocket was performed to highlight their scores, mode of binding and the important interactions to the amino acid residues of the enzyme...
March 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28290249/in-vitro-and-in-silico-studies-of-mangiferin-from-aphloia-theiformis-on-key-enzymes-linked-to-diabetes-type-2-and-associated-complications
#12
Mohamad F Mahomoodally, Simone Carradori, Azzurra Stefanucci, Adriano Mollica, Gokhan Zengin, Marie C N Picot
BACKGROUND: Mangiferin, was identified in the crude methanol extract, ethyl acetate, and n-butanol fractions of Aphloia theiformis (Vahl.) Benn. OBJECTIVE: To study the plausible binding modes of mangiferin to key enzymes linked to diabetes type 2 (DT2), obesity, hypertension, Alzheimer's disease, and urolithiasis using molecular docking. METHOD: Crystallographic structures of α-amylase, α-glucosidase, glycogen phosphorylase (GP), pancreatic lipase, cholesterol esterase (CEase), angiotensin-I-converting enzyme (ACE), acetyl cholinesterase (AChE), and urease available on the Protein Databank database were docked to mangiferin using Gold 6...
March 7, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28287700/price-for-opening-the-transient-specificity-pocket-in-human-aldose-reductase-upon-ligand-binding-structural-thermodynamic-kinetic-and-computational-analysis
#13
Chris Rechlin, Frithjof Scheer, Felix Terwesten, Tobias Wulsdorf, Ewa Pol, Veronica Fridh, Philipp Toth, Wibke E Diederich, Andreas Heine, Gerhard Klebe
Insights into the thermodynamic and kinetic signature of the transient opening of a protein-binding pocket are presented resulting from accommodation of suitable substituents attached to a given parent ligand scaffold. As target, we selected human aldose reductase, an enzyme involved in development of late-stage diabetic complications. To recognize a large scope of substrate molecules, this reductase opens a transient specificity pocket. The pocket-opening step was studied by X-ray crystallography, microcalorimetry and surface plasmon resonance using a narrow series of 2-carbamoyl-phenoxy-acetic acid derivatives...
March 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28282632/evaluation-of-the-combination-mode-of-azoles-antifungal-inhibitors-with-cacyp51-and-the-influence-of-site-directed-mutation
#14
Bin Sun, Wanxu Huang, Min Liu
14α-demethylase (CYP51) is an essential metabolic enzyme for fungal survival and has been considered as an interesting target for the development of new antifungal inhibitors. Azoles antifungal inhibitors in the treatment of fungal diseases are good candidates via the interaction with the target enzyme CYP51 of fungus. In the study, we constructed the homology model for Candida albicans CYP51 (CACYP51) and analyzed the active site. In order to better understand the structural characteristics of azoles inhibitors and combination mode, the common feature pharmacophore model and the molecular docking were performed...
February 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28278765/antimycobacterial-docking-and-molecular-dynamic-studies-of-pentacyclic-triterpenes-from-buddleja-saligna-leaves
#15
Alveera Singh, Katharigatta N Venugopala, Mohammed A Khedr, Mellendran Pillay, Kenneth U Nwaeze, Yacoob Coovadia, Francis Shode, Bharti Odhav
Buddleja saligna (family Buddlejaceae) is a medicinal plant endemic to South Africa. Two isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were isolated from the leaves of B. saligna using silica gel column chromatography. Compounds oleanolic acid and ursolic acid were subjected to derivatization with acetic anhydride in the presence of pyridine to obtain oleanolic acid-3-acetate and ursolic acid-3-acetate, respectively. The structures of these compounds were fully characterized by detailed nuclear magnetic resonance (NMR) investigations, which included (1)H and (13)C NMR...
September 22, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28278760/computational-characterization-of-residue-couplings-and-micropolymorphism-induced-changes-in-the-dynamics-of-two-differentially-disease-associated-human-mhc-class-i-alleles
#16
Onur Serçinoğlu, Pemra Ozbek
Human major histocompatibility complex class I (MHC I) - or human leukocyte antigen (HLA) - proteins present intracellularly processed peptides to cytotoxic T lymphocytes in the adaptive immune response to pathogens. A high level of polymorphism in human MHC I proteins defines the peptide-binding specificity of thousands of different MHC alleles. However, polymorphism as well as the peptide ligand can also affect the global dynamics of the complex. In this study, we conducted classical molecular dynamics simulations of two HLA alleles, the ankylosing spondylitis (AS) associated/tapasin-dependent HLA-B*27:05 and nondisease-associated/tapasin-independent HLA-B*27:09, both in peptide-free forms as well as complex with four different peptides ligands...
March 1, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28274117/self-assembly-nanostructures-of-triglyceride-water-interfaces-determine-functional-conformations-of-candida-antarctica-lipase-b
#17
Sven P Benson, Juergen Pleiss
Candida antarctica lipase B (CalB) acts as a lipase when adsorbed to an acylglyceride interface and as an esterase when exposed to aqueous environment. The effect of the molecular self-assembly nanostructure of triglyceride-water interfaces on structural conformations of adsorbed CalB and the implications to its catalytic function were studied by molecular dynamics simulations. Systems of CalB adsorbed to interfaces and solvated in water were compared. The two environments induced relative motions of helices α5 and α10 that resulted in open and closed conformations...
March 8, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28274039/evaluation-of-gengigel%C3%A2-application-in-the-management-of-furcation-with-coronally-advanced-flap-through-surgical-re-entry-a-split-mouth-clinical-study
#18
Sugandha Gupta, Suresh D Kediege, Akanksha Gupta, Kanu Jain
INTRODUCTION: One of the challenging and unique periodontal problem of Grade II furcation defect has been managed through different treatment modalities in the past. A successful approach is based on complete closure of the defect. Different regenerative approaches have been tried. AIM: This study was carried out with an aim to evaluate the role of Gengigel® (0.8% hyaluronic acid) as a potential material for regeneration of lost attachment apparatus. MATERIALS AND METHODS: A total of 20 sites with Grade II furcation defects from 10 patients were selected using random sampling technique...
January 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28272861/analysis-of-the-glutamate-agonist-ly404-039-binding-to-nonstatic-dopamine-receptor-d2-dimer-structures-and-consensus-docking
#19
Ramin Ekhteiari Salmas, Philip Seeman, Busecan Aksoydan, Ismail Erol, Isik Kantarcioglu, Matthias Stein, Mine Yurtsever, Serdar Durdagi
Dopamine receptor D2 (D2R) plays an important role in the human central nervous system and is a focal target of antipsychotic agents. The D2(High)R and D2(Low)R dimeric models previously developed by our group are used to investigate the prediction of binding affinity of the LY404,039 ligand and its binding mechanism within the catalytic domain. The computational data obtained using molecular dynamics simulations fit well with the experimental results. The calculated binding affinities of LY404,039 using MM/PBSA for the D2(High)R and D2(Low)R targets were -12...
March 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28272449/design-and-functional-characterization-of-a-novel-abscisic-acid-analog
#20
Xiaoqiang Han, Lun Jiang, Chuanliang Che, Chuan Wan, Huizhe Lu, Yumei Xiao, Yanjun Xu, Zhongzhou Chen, Zhaohai Qin
The phytohormone abscisic acid (ABA) plays a crucial role in mediating plant growth and development by recruiting genetically redundant ABA receptors. To overcome its oxidation inactivation, we developed a novel ABA analog named 2',3'-benzo-iso-ABA (iso-PhABA) and studied its function and structural characterization with A. thaliana ABA receptors. The (+)-iso-PhABA form showed much higher ABA-like activities than (+)-ABA including inhibitory effects on the seed germination of lettuce and A. thaliana, wheat embryo germination and rice seedling elongation...
March 8, 2017: Scientific Reports
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