Consensus of Sample-Balanced Classifiers for Identifying Ligand-Binding Residue by Co-evolutionary Physicochemical Characteristics of Amino Acids

2013 ◽  
pp. 206-212
Author(s):  
Peng Chen
Keyword(s):  
Amino Acids ◽  
Ligand Binding ◽  
Physicochemical Characteristics ◽  
Binding Residue

Common modifications of selenocysteine in selenoproteins

2019 ◽  
Vol 64 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Elias S.J. Arnér
Keyword(s):  
Amino Acids ◽  
Covalent Binding ◽  
Physicochemical Characteristics ◽  
Redox Active

Abstract Selenocysteine (Sec), the sulfur-to-selenium substituted variant of cysteine (Cys), is the defining entity of selenoproteins. These are naturally expressed in many diverse organisms and constitute a unique class of proteins. As a result of the physicochemical characteristics of selenium when compared with sulfur, Sec is typically more reactive than Cys while participating in similar reactions, and there are also some qualitative differences in the reactivities between the two amino acids. This minireview discusses the types of modifications of Sec in selenoproteins that have thus far been experimentally validated. These modifications include direct covalent binding through the Se atom of Sec to other chalcogen atoms (S, O and Se) as present in redox active molecular motifs, derivatization of Sec via the direct covalent binding to non-chalcogen elements (Ni, Mb, N, Au and C), and the loss of Se from Sec resulting in formation of dehydroalanine. To understand the nature of these Sec modifications is crucial for an understanding of selenoprotein reactivities in biological, physiological and pathophysiological contexts.

Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Amir Taherkhani ◽  
Athena Orangi ◽  
Shirin Moradkhani ◽  
Zahra Khamverdi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Amino Acid ◽  
Matrix Metalloproteinase ◽  
Ligand Binding ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Dimensional Structure ◽  
Control Test ◽  
Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

scholarly journals Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor

2003 ◽  
Vol 371 (2) ◽  
pp. 443-449 ◽  
Author(s):  
Frank NEUSCHÄFER-RUBE ◽  
Eva ENGEMAIER ◽  
Sina KOCH ◽  
Ulrike BÖER ◽  
Gerhard P. PÜSCHEL
Keyword(s):  
Amino Acids ◽  
Ligand Binding ◽  
G Protein ◽  
Transmembrane Domain ◽  
Sequence Similarity ◽  
Membrane Receptors ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Receptor Subtypes ◽  
Plasma Membrane Receptors

Prostanoid receptors belong to the class of heptahelical plasma membrane receptors. For the five prostanoids, eight receptor subtypes have been identified. They display an overall sequence similarity of roughly 30%. Based on sequence comparison, single amino acids in different subtypes of different species have previously been identified by site-directed mutagenesis or in hybrid receptors that appear to be essential for ligand binding or G-protein coupling. Based on this information, a series of mutants of the human FP receptor was generated and characterized in ligand-binding and second-messenger-formation studies. It was found that mutation of His-81 to Ala in transmembrane domain 2 and of Arg-291 to Leu in transmembrane domain 7, which are putative interaction partners for the prostanoid's carboxyl group, abolished ligand binding. Mutants in which Ser-263 in transmembrane domain 6 or Asp-300 in transmembrane domain 7 had been replaced by Ala or Gln, respectively, no longer discriminated between prostaglandins PGF2α and PGD2. Thus distortion of the topology of transmembrane domains 6 and 7 appears to interfere with the cyclopentane ring selectivity of the receptor. PGF2α-induced inositol formation was strongly reduced in the mutant Asp-300Gln, inferring a role for this residue in agonist-induced G-protein activation.

Key Amino Acids in the γ Subunit of the γ-Aminobutyric AcidA Receptor that Determine Ligand Binding and Modulation at the Benzodiazepine Site

1997 ◽  
Vol 52 (5) ◽  
pp. 874-881 ◽  
Author(s):  
Peter B. Wingrove ◽  
Sally A. Thompson ◽  
Keith A. Wafford ◽  
Paul J. Whiting
Keyword(s):  
Amino Acids ◽  
Ligand Binding ◽  
Γ Subunit ◽  
Benzodiazepine Site

scholarly journals Assessment of ligand-binding residue predictions in CASP9

2011 ◽  
Vol 79 (S10) ◽  
pp. 126-136 ◽  
Author(s):  
Tobias Schmidt ◽  
Jürgen Haas ◽  
Tiziano Gallo Cassarino ◽  
Torsten Schwede
Keyword(s):  
Ligand Binding ◽  
Binding Residue

scholarly journals Unique functional properties of a member of the Fushi Tarazu-Factor 1 family from Schistosoma mansoni

2004 ◽  
Vol 382 (1) ◽  
pp. 337-351 ◽  
Author(s):  
Benjamin BERTIN ◽  
Souphatta SASORITH ◽  
Stéphanie CABY ◽  
Frédérik OGER ◽  
Jocelyne CORNETTE ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ligand Binding ◽  
Schistosoma Mansoni ◽  
Transcriptional Activity ◽  
Binding Pocket ◽  
Activation Function ◽  
Orphan Receptor ◽  
Fushi Tarazu ◽  
Dependent Activity ◽  
Arginine Residues

SmFtz-F1 (Schistosoma mansoni Fushi Tarazu-Factor 1) belongs to the Ftz-F1 subfamily of nuclear receptors, but displays marked structural differences compared with its mammalian homologues SF-1 (steroidogenic factor-1) or liver receptor homologue-1. These include a long F domain (104 amino acids), an unusually large hinge region (133 amino acids) and a poorly conserved E-domain. Here, using Gal4 constructs and a mammalian two-hybrid assay, we have characterized the roles of these specific regions both in the transcriptional activity of the receptor and in its interactions with cofactors. Our results have shown that, although the AF-2 (activation function-2) region is the major activation function of the receptor, both the F and D domains are essential for AF-2-dependent activity. Modelling of SmFtz-F1 LBD (ligand-binding domain) and structure-guided mutagenesis allowed us to show the important role of helix H1 in maintaining the structural conformation of the LBD, and suggested that its autonomous transactivation activity, also observed with SF-1, is fortuitous. This strategy also allowed us to study an eventual ligand-dependence for this orphan receptor, the predicted three-dimensional models suggesting that the SmFtz-F1 LBD contains a large and well-defined ligand-binding pocket sealed by two arginine residues orientated towards the interior of the cavity. Mutation of these two residues provoked a loss of transcriptional activity of the receptor, and strongly reduced its interaction with SRC1 (steroid receptor cofactor-1), suggesting a ligand-dependent activity for SmFtz-F1. Taken together, our results argue for original and specific functional activities for this platyhelminth nuclear receptor.

Meat quality and chemical assessment of porcine longissimus dorsi within different muscle pH

2019 ◽  
Vol 59 (6) ◽  
pp. 1155 ◽  
Author(s):  
D. R. Kang ◽  
S. A. Belal ◽  
E. S. R. Cho ◽  
H. N. Kang ◽  
J. H. Jung ◽  
...  
Keyword(s):  
Amino Acids ◽  
Adenosine Diphosphate ◽  
Physicochemical Characteristics ◽  
Low Ph ◽  
Eating Quality ◽  
Longissimus Dorsi ◽  
Pork Quality ◽  
Isoleucine Leucine ◽  
High Ph ◽  
Longissimus Dorsi Muscle

This study was carried out to investigate the influence of pH on the Berkshire’s pork longissimus dorsi muscle, by comparing physicochemical characteristics in a high pH group (5.92 ± 0.02) and a low pH group (5.55 ± 0.03) on the basis of muscle pH24 h post-mortem. Fifteen pigs were assigned to each group (n = 15). The low pH group showed higher filter-paper fluid uptake, cooking loss and National Pork Producers Council marbling scores but did not significantly differ from the high pH group (P > 0.05). The low pH group also showed higher Commission International de l’Eclairage L* and b*, drip loss, and shearing forces were significantly different from the high pH group. However, Commission International de l’Eclairage meat colour value (a*) and National Pork Producers Council colour were higher in the high pH group. The content of glutamic acid, threonine, and serine amino acids associated with a good flavour was higher in the high pH group. Also, amino acids associated with a bitter or poor flavour, such as valine, isoleucine, leucine, tyrosine, and histidine, was higher in the high pH group as well. The taste of umami was significantly (P < 0.01) higher in the high pH group. Levels of the nucleotide compounds hypoxanthine and inosine tended to be higher (P < 0.05) in the high pH group, whereas adenosine diphosphate levels were increased in the low pH group (P < 0.05). It is concluded that pH of pork could be a good indicator of pork quality and related to factors influencing pork eating quality. As pH of pork is not only positively associated with physical traits of pork but also closely related to chemical traits of which higher free amino acids and nucleotides enhance pork quality.

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