scholarly journals THE APPLICABILITY OF THE CRYSTAL STRUCTURE OF TERMOTOGA MARITIMA 4--GLUCANOTRANSFERASE AS THE TEMPLATE FOR SULOCHRIN AS -GLUCOSIDASE INHIBITORS

2010 ◽  
Vol 9 (3) ◽  
pp. 479-486
Author(s):  
Rizna Triana Dewi ◽  
Yulia Anita ◽  
Enade Perdana Istyastono ◽  
Akhmad Darmawan ◽  
Muhamad Hanafi
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Thermotoga Maritima ◽  
Binding Pocket ◽  
Operating Environment ◽  
High Sequence Identity ◽  
Glucosidase Inhibitor ◽  
Glucosidase Inhibitors ◽  
Docking Method ◽  
Binding Residues

Interaction of sulochrin to active site of glucosidase enzyme of Termotoga maritime has been studied by employing docking method using Molecular Operating Environment (MOE), in comparison with those are reports of established inhibitor α-glucosidase such as acarbose, miglitol and voglibose, and salicinol, as reference compounds. The crystal structure T. maritima α-glucanotransferase (PDB code: 1LWJ) can be employed to serve as the template in the virtual screening of S. cerevisiae α-glucosidase. The comparison between the binding pocket residues of Thermotoga maritima α-glucanotransferase and Saccharomyces cerevisiae α-glucosidase show a high sequence identity and similarity. The result showed that sulochrin could be located in the binding pocket and formed some interactions with the binding residues. The ligands showed proper predicted binding energy (-6.74 - -4.13 kcal/mol) and predicted Ki values (0.011 - 0.939 mM). Sulochrin has a possibility to serve as a lead compound in the development of new α-glucosidase inhibitor.   Keywords: Docking, sulochrin, α-glucosidase Inhibitor, Thermotoga maritime α-glucotransferase, Saccharomyces cerevisiae α-glucosidase, MOE

scholarly journals Docking Sulochrin and Its Derivative as α-Glucosidase Inhibitors of Saccharomyces cerevisiae

2017 ◽  
Vol 17 (1) ◽  
pp. 144 ◽  
Author(s):  
Wening Lestari ◽  
Rizna Triana Dewi ◽  
Leonardus Broto Sugeng Kardono ◽  
Arry Yanuar
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Hydrogen Bonds ◽  
Active Site ◽  
Iodine Atom ◽  
Glucosidase Inhibitors ◽  
Docking Method ◽  
Better Than

Sulochrin is known to have an activity as inhibitors of the α-glucosidase enzyme. In this report interaction of sulochrin to the active site of the α-glucosidase enzyme from Saccharomyces cerevisiae was studied by docking method. The crystal structure of α-glucosidase from S. cerevisiae obtained from the homology method using α-glucosidase from S. cerevisiae (Swiss-Prot code P53341) as a target and crystal structure of isomaltase from S. cerevisiae (PDB code 3A4A) as a template. These studies show that sulochrin and sulochrin-I could be bound in the active site of α-glucosidase from S. cerevisiae through the formation of hydrogen bonds with Arg213, Asp215, Glu277, Asp352. Sulochrin-I has stability and inhibition of the α-glucosidase enzyme better than sulochrin. The iodine atom in the structure of sulochrin can increase the activity as an inhibitor of the α-glucosidase enzyme.

scholarly journals Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer

2016 ◽  
Vol 113 (34) ◽  
pp. 9635-9640 ◽  
Author(s):  
Nikolaos Kouvatsos ◽  
Petros Giastas ◽  
Dafni Chroni-Tzartou ◽  
Cornelia Poulopoulou ◽  
Socrates J. Tzartos
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Structural Information ◽  
Extracellular Domain ◽  
Binding Pocket ◽  
Nachr Subunit ◽  
Homologous Proteins ◽  
High Sequence Identity ◽  
Neuronal Nachr ◽  
Low Sensitivity

In this study we report the X-ray crystal structure of the extracellular domain (ECD) of the human neuronal α2 nicotinic acetylcholine receptor (nAChR) subunit in complex with the agonist epibatidine at 3.2 Å. Interestingly, α2 was crystallized as a pentamer, revealing the intersubunit interactions in a wild type neuronal nAChR ECD and the full ligand binding pocket conferred by two adjacent α subunits. The pentameric assembly presents the conserved structural scaffold observed in homologous proteins, as well as distinctive features, providing unique structural information of the binding site between principal and complementary faces. Structure-guided mutagenesis and electrophysiological data confirmed the presence of the α2(+)/α2(−) binding site on the heteromeric low sensitivity α2β2 nAChR and validated the functional importance of specific residues in α2 and β2 nAChR subunits. Given the pathological importance of the α2 nAChR subunit and the high sequence identity with α4 (78%) and other neuronal nAChR subunits, our findings offer valuable information for modeling several nAChRs and ultimately for structure-based design of subtype specific drugs against the nAChR associated diseases.

scholarly journals Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yufei Han ◽  
Qian Zhuang ◽  
Bo Sun ◽  
Wenping Lv ◽  
Sheng Wang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Biochemical Characterization ◽  
Substrate Binding ◽  
Binding Pocket ◽  
Substrate Binding Pocket ◽  
Transmembrane Segments ◽  
Therapeutic Molecules ◽  
Binding Cavity ◽  
Immune System Regulation ◽  
Mediated Reduction

AbstractSteroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-Δ4 structure, such as testosterone or progesterone, are catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which are essential for multiple physiological and pathological processes. SRD5A2 is already a target of clinically relevant drugs. However, the detailed mechanism of SRD5A-mediated reduction remains elusive. Here we report the crystal structure of PbSRD5A from Proteobacteria bacterium, a homolog of both SRD5A1 and SRD5A2, in complex with the cofactor NADPH at 2.0 Å resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic substrate binding cavity, whereas TM5-7 coordinate cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and -2, together with biochemical characterization, define the substrate binding pocket of SRD5As, explain the properties of disease-related mutants and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-Δ4 reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible.

scholarly journals Characterization of the Acetate Binding Pocket in the Methanosarcina thermophila Acetate Kinase

2005 ◽  
Vol 187 (7) ◽  
pp. 2386-2394 ◽  
Author(s):  
Cheryl Ingram-Smith ◽  
Andrea Gorrell ◽  
Sarah H. Lawrence ◽  
Prabha Iyer ◽  
Kerry Smith ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Binding Pocket ◽  
Acetate Kinase ◽  
Phosphoryl Group ◽  
Acetyl Phosphate ◽  
Hydrophobic Pocket ◽  
Methanosarcina Thermophila ◽  
Methyl Group ◽  
Substrate Binding Sites

ABSTRACT Acetate kinase catalyzes the reversible magnesium-dependent synthesis of acetyl phosphate by transfer of the ATP γ-phosphoryl group to acetate. Inspection of the crystal structure of the Methanosarcina thermophila enzyme containing only ADP revealed a solvent-accessible hydrophobic pocket formed by residues Val93, Leu122, Phe179, and Pro232 in the active site cleft, which identified a potential acetate binding site. The hypothesis that this was a binding site was further supported by alignment of all acetate kinase sequences available from databases, which showed strict conservation of all four residues, and the recent crystal structure of the M. thermophila enzyme with acetate bound in this pocket. Replacement of each residue in the pocket produced variants with Km values for acetate that were 7- to 26-fold greater than that of the wild type, and perturbations of this binding pocket also altered the specificity for longer-chain carboxylic acids and acetyl phosphate. The kinetic analyses of variants combined with structural modeling indicated that the pocket has roles in binding the methyl group of acetate, influencing substrate specificity, and orienting the carboxyl group. The kinetic analyses also indicated that binding of acetyl phosphate is more dependent on interactions of the phosphate group with an unidentified residue than on interactions between the methyl group and the hydrophobic pocket. The analyses also indicated that Phe179 is essential for catalysis, possibly for domain closure. Alignments of acetate kinase, propionate kinase, and butyrate kinase sequences obtained from databases suggested that these enzymes have similar catalytic mechanisms and carboxylic acid substrate binding sites.

scholarly journals Crystal structure of an α/β serine hydrolase (YDR428C) from Saccharomyces cerevisiae at 1.85 Å resolution

2004 ◽  
Vol 58 (3) ◽  
pp. 755-758 ◽  
Author(s):  
Joseph W. Arndt ◽  
Robert Schwarzenbacher ◽  
Rebecca Page ◽  
Polat Abdubek ◽  
Eileen Ambing ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Serine Hydrolase

Crystal Structure of Full Length Topoisomerase I from Thermotoga maritima

2006 ◽  
Vol 358 (5) ◽  
pp. 1328-1340 ◽  
Author(s):  
Guido Hansen ◽  
Axel Harrenga ◽  
Bernd Wieland ◽  
Dietmar Schomburg ◽  
Peter Reinemer
Keyword(s):  
Crystal Structure ◽  
Topoisomerase I ◽  
Thermotoga Maritima ◽  
Full Length

scholarly journals The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8

2004 ◽  
Vol 9 (7) ◽  
pp. 611-618 ◽  
Author(s):  
Kenji Sugawara ◽  
Nobuo N. Suzuki ◽  
Yuko Fujioka ◽  
Noboru Mizushima ◽  
Yoshinori Ohsumi ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Light Chain ◽  
Mammalian Homologue
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