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https://www.readbyqxmd.com/read/29156293/fe-iii-sulfide-interaction-in-globins-characterization-and-quest-for-a-putative-fe-iv-sulfide-species
#1
Augustin C Mot, Cristina Bischin, Grigore Damian, Amr A A Attia, Emese Gal, Nicoleta Dina, Nicolae Leopold, Radu Silaghi-Dumitrescu
The present study reports findings regarding the contrast between H2S interaction with bovine hemoglobin (Hb) and horse heart myoglobin (Mb), in terms of binding and dissociation kinetics, affinities, and mechanism. At pH9.5, oxidation of ferric-sulfide adducts in presence of no free sulfide, using hexachloroiridate as oxidant is examined using stopped-flow UV-vis, EPR, vibrational spectroscopy and mass spectrometry. Oxidation of the ferric-sulfide adduct in such conditions occurs with a putative unstable Fe(IV)-sulfide adduct as intermediate that finally leads to a paramagnetic ferric species with distinct EPR features...
November 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29153506/role-of-non-local-interactions-between-cdr-loops-in-binding-affinity-of-mr78-antibody-to-marburg-virus-glycoprotein
#2
Amandeep K Sangha, Jinhui Dong, Lauren Williamson, Takao Hashiguchi, Erica Ollmann Saphire, James E Crowe, Jens Meiler
An atomic-detail model of the Marburg virus glycoprotein in complex with a neutralizing human monoclonal antibody designated MR78 was constructed using Phenix.Rosetta starting from a 3.6Å crystallographic density map. The Asp at T6 in the HCDR3's bulged torso cannot form the canonical salt bridge as position T2 lacks an Arg or Lys residue. It instead engages in a hydrogen bond interaction with a Tyr contributed by the HCDR1 loop. This inter-CDR loop interaction stabilizes the bulged conformation needed for binding to the viral glycoprotein: a Tyr to Phe mutant displays a binding affinity reduced by a factor of at least 10...
November 14, 2017: Structure
https://www.readbyqxmd.com/read/29152051/%C3%AF-space-screening-of-dermorphin-based-tetrapeptides-through-use-of-constrained-arylazepinone-and-quinolinone-scaffolds
#3
Olivier Van der Poorten, Robin Van Den Hauwe, Emilie Eiselt, Cecilia Betti, Karel Guillemyn, Nga N Chung, François Hallé, Frédéric Bihel, Peter W Schiller, Dirk Tourwé, Philippe Sarret, Louis Gendron, Steven Ballet
Herein, the synthesis of novel conformationally constrained amino acids, 4-amino-8-bromo-2-benzazepin-3-one (8-Br-Aba), 3-amino-3,4-dihydroquinolin-2-one, and regioisomeric 4-amino-naphthoazepinones (1- and 2-Ana), is described. Introduction of these constricted scaffolds into the N-terminal tetrapeptide of dermorphin (i.e., H-Tyr-d-Ala-Phe-Gly-NH2) induced significant shifts in binding affinity, selectivity, and in vitro activity at the μ- and δ-opioid receptors (MOP and DOP, respectively). A reported constrained μ-/δ-opioid lead tetrapeptide H-Dmt-d-Arg-Aba-Gly-NH2 was modified through application of various constrained building blocks to identify optimal spatial orientations in view of activity at the opioid receptors...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29149994/a-novel-fluorescence-biosensor-for-sensitivity-detection-of-tyrosinase-and-acid-phosphatase-based-on-nitrogen-doped-graphene-quantum-dots
#4
Zhengyi Qu, Weidan Na, Xiaotong Liu, Hua Liu, Xingguang Su
In this paper, we developed a sensitive fluorescence biosensor for tyrosinase (TYR) and acid phosphatase (ACP) activity detection based on nitrogen-doped graphene quantum dots (N-GQDs). Tyrosine could be catalyzed by TYR to generate dopaquinone, which could efficiently quench the fluorescence of N-GQDs, and the degree of fluorescence quenching of N-GQDs was proportional to the concentration of TYR. In the presence of ACP, l-Ascorbic acid-2-phosphate (AAP) was hydrolyzed to generate ascorbic acid (AA), and dopaquinone was reduced to l-dopa, resulting in the fluorescence recovery of the quenched fluorescence by dopaquinone...
January 2, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29146868/vasohibins-svbp-are-tubulin-carboxypeptidases-tcp-that-regulate-neuron-differentiation
#5
Chrystelle Aillaud, Christophe Bosc, Leticia Peris, Anouk Bosson, Pierre Heemeryck, Juliette Van Dijk, Julien Le Friec, Benoit Boulan, Frédérique Vossier, Laura E Sanman, Salahuddin Syed, Neri Amara, Yohann Couté, Laurence Lafanechère, Eric Denarier, Christian Delphin, Laurent Pelletier, Sandrine Humbert, Matthew Bogyo, Annie Andrieux, Krzysztof Rogowski, Marie-Jo Moutin
Reversible detyrosination of α-tubulin is crucial to microtubule dynamics and functions and defects have been implicated in cancer, brain disorganization, and cardiomyopathies. The identity of the tubulin tyrosine carboxypeptidase (TCP) responsible for detyrosination has remained unclear. We used chemical proteomics with a potent unique irreversible inhibitor to show that the major brain TCP is a complex of vasohibin-1 (VASH1) with the Small Vasohibin Binding Protein (SVBP). VASH1 and its homolog VASH2, when complexed with SVBP, exhibited robust and specific Tyr/Phe carboxypeptidase activity on microtubules...
November 16, 2017: Science
https://www.readbyqxmd.com/read/29146597/structure-guided-engineering-of-the-substrate-specificity-of-a-fungal-%C3%AE-glucuronidase-toward-triterpenoid-saponins
#6
Bo Lv, Hanli Sun, Shen Huang, Xudong Feng, Tao Jiang, Chun Li
Glycoside hydrolases (GHs) have attracted special attention in research aimed at modifying natural products by partial removal of sugar moieties to manipulate their solubility and efficacy. However, these modifications are challenging to control because the low substrate specificity of most GHs often generates undesired by-products. We previously identified a GH2-type fungal β-glucuronidase from Aspergillus oryzae (PGUS) exhibiting promiscuous substrate specificity in hydrolysis of triterpenoid saponins. Here, we present the PGUS structure, representing the first structure of a fungal β-glucuronidase, and of an inactive PGUS mutant in complex with the native substrate glycyrrhetic acid 3-O-mono-β- glucuronide (GAMG)...
November 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29146558/role-of-his-his-interaction-in-ser-474-his-475-tyr-476-sequence-of-chondroitinase-abc-i-in-the-enzyme-activity-and-stability
#7
Monireh Maleki, Khosro Khajeh, Massoud Amanlou, Abolfazl Golestani
Despite clinical importance of chondroitinase ABC I, its application has been limited due to thermal instability as reported in the literature. There are various approaches to improve thermal stability of enzymes, among them, His-His interactions are believed generally as an effective means. In the present study and for preparing a His-His interaction, various mutations in the sequence of Ser(474)-His(475)-Tyr(476) at catalytic domain of the enzyme were performed using site directed mutagenesis method. The effect of these mutations on activity, stability and structural features of cABC I was assessed...
November 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29145845/network-pharmacological-mechanisms-of-vernonia-anthelmintica-l-in-the-treatment-of-vitiligo-isorhamnetin-induction-of-melanogenesis-via-up-regulation-of-melanin-biosynthetic-genes
#8
Ji Ye Wang, Hong Chen, Yin Yin Wang, Xiao Qin Wang, Han Ying Chen, Mei Zhang, Yun Tang, Bo Zhang
BACKGROUND: Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin. The current therapeutic approaches are limited. Although the anti-vitiligo mechanisms of Vernonia anthelmintica (L.) remain ambiguous, the herb has been broadly used in Uyghur hospitals to treat vitiligo. The overall objective of the present study aims to identify the potential lead compounds from Vernonia anthelmintica (L.) in the treatment of vitiligo via an oral route as well as the melanogenic mechanisms in the systematic approaches in silico of admetSAR and substructure-drug-target network-based inference (SDTNBI)...
November 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29143197/three-cases-of-hereditary-tyrosinaemia-type-1-neuropsychiatric-outcomes-and-brain-imaging-following-treatment-with-ntbc
#9
Helen Walker, Mervi Pitkanen, Yusof Rahman, Sally F Barrington
AIM: To examine neuropsychiatric outcomes in adults with hereditary tyrosinaemia type I (HT-1), treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and correlate these with functional imaging as well as with tyrosine and phenylalanine-tyrosine (Phe:Tyr) ratios. DESIGN: We retrospectively reviewed the medical records of three adult HT-1 patients with a particular focus on their FDG PET/CT brain scans, neuropsychiatric assessment (including neurocognitive assessment and mood and anxiety ratings) as well as mean tyrosine and phenylalanine levels and Phe:Tyr ratios for 3-month period...
November 16, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29139109/%C3%AE-cyclodextrin-encapsulated-polyphenols-as-effective-antioxidants
#10
Pritam Roy, Amit Kumar Dinda, Susmitnarayan Chaudhury, Swagata Dasgupta
Formation of dityrosine (DT) cross-linkages in proteins is one of the most widely used markers of oxidative stress. Ribonuclease A (RNase A) has 6 Tyr residues and shows a characteristic DT fluorescence peak upon oxidation in addition to major changes in its secondary structure. DT formation can be prevented by using polyphenols (GA, ECG, and EGCG) which are known to have strong antioxidant activity. However, it has been observed that ECG and EGCG initiate protein oligomerization due to protein-polyphenol cross-linkages...
November 15, 2017: Biopolymers
https://www.readbyqxmd.com/read/29138021/gyra-and-or-parc-alterations-of-haemophilus-influenzae-strains-isolated-from-the-urethra-of-men-with-acute-urethritis
#11
Hiromi Kondo, Shin Ito, Kyoko Hatazaki, Kengo Horie, Keita Nakane, Kosuke Mizutani, Tomohiro Tsuchiya, Mitsuru Yasuda, Shigeaki Yokoi, Masahiro Nakano, Takashi Deguchi
Of 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with urogenital infections, we enrolled 6 strains (8.2%) with levofloxacin (LVFX) minimum inhibitory concentrations (MICs) of ≥0.03 μg/ml in this study. All the strains were isolated from non-gonococcal urethritis (NGU). We amplified the quinolone resistance-determining region of the gyrA gene and the analogous region of the parC gene from bacterial DNAs by PCR and sequenced the PCR products. Two strains with a LVFX MIC of 0...
November 11, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29131958/design-synthesis-and-biological-assessment-of-biased-allosteric-modulation-of-the-urotensin-ii-receptor-using-achiral-1-3-4-benzotriazepin-2-one-turn-mimics
#12
Antoine Douchez, Étienne Billard, Terence Hébert, David Chatenet, William D Lubell
Benzotriazepin-2-ones were designed to mimic the suggested bioactive γ-turn conformation of the Bip-Lys-Tyr tripeptide in Urocontrin ([Bip(4)]URP), which modulates the urotensin II receptor (UT) and differentiates the effects of the endogenous ligands urotensin II (UII) and urotensin II-related peptide (URP). Twenty-six benzotriazepin-2-ones were synthesized by acylation of anthranilate-derived amino ketones with an aza-glycine equivalent, chemoselective nitrogen functionalization and ring closure. Several mimics exhibited selective modulatory effects on hUII- and URP-associated vasoconstriction in an ex-vivo rat aortic ring bioassay...
November 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29130461/intracellular-coassembly-boosts-the-anti-inflammation-capacity-of-dexamethasone
#13
Wei Tang, Jingbo Yang, Zhibin Zhao, Zhexiong Lian, Gaolin Liang
Dexamethasone (Dex) is one of the essential medicines used to treat inflammation diseases but an overdose of Dex leads to severe adverse effects. The development of a new strategy to boost the anti-inflammation efficacy of Dex is, therefore, important but remains challenging. Herein, by employing an enzyme-instructed self-assembly system, we developed an intracellular coassembly strategy to boost the anti-inflammation efficacy of Dex. Under the catalysis of alkaline phosphatase (ALP), the hydrogelator precursor Nap-Phe-Phe-Tyr(H2PO3)-OH (1p) self-assembled to form Gel 1 but dexamethasone sodium phosphate (Dp) only yielded Dex precipitates...
November 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/29130148/interaction-of-zearalenone-with-bovine-serum-albumin-as-determined-by-fluorescence-quenching
#14
Liang Ma, Chris M Maragos, Yuhao Zhang
The major aim of this study was to examine the binding of zearalenone (ZEN) to bovine serum albumin (BSA) by measuring the quenching of the intrinsic fluorescence of the protein under aqueous conditions. The results suggest that ZEN has a strong ability to quench the intrinsic fluorescence of BSA through a static mechanism. The hydrophobicity of the microenvironment around the tyrosine (Tyr) residues in BSA was increased in the presence of ZEN. The quenching constants, ratio of protein with ZEN, and thermodynamic parameters were determined...
November 13, 2017: Mycotoxin Research
https://www.readbyqxmd.com/read/29129605/evolution-and-adaptation-of-single-pass-transmembrane-proteins
#15
Irina D Pogozheva, Andrei L Lomize
A comparative analysis of 6,039 single-pass (bitopic) membrane proteins from six evolutionarily distant organisms was performed based on data from the Membranome database. The observed repertoire of bitopic proteins is significantly enlarged in eukaryotic cells and especially in multicellular organisms due to the diversification of enzymes, emergence of proteins involved in vesicular trafficking, and expansion of receptors, structural, and adhesion proteins. The majority of bitopic proteins in multicellular organisms are located in the plasma membrane (PM) and involved in cell communication...
November 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29128397/identification-and-characterization-of-molluscan-caveolin-1-ortholog-from-haliotis-discus-discus-possible-involvement-in-embryogenesis-and-host-defense-mechanism-against-pathogenic-stress
#16
H M V Udayantha, S D N K Bathige, Thanthrige Thiunuwan Priyathilaka, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Caveolins are principal membrane proteins of caveolae that play a central role in signal transduction, substrate transport, and membrane trafficking in various cell types. Numerous studies have reported the crucial role of caveolin-1 (CAV1) in response to invading microbes; yet, very little is known about molluscan CAV1. In this study, we identified and characterized CAV1 ortholog from the disk abalone, Haliotis discus discus (HdCAV1). The cDNA sequence of HdCAV1 is 826 bp long and encodes a 127-amino acid polypeptide...
November 8, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29128310/position-specific-contribution-of-interface-tryptophans-on-membrane-protein-energetics
#17
Deepti Chaturvedi, Radhakrishnan Mahalakshmi
Interface tryptophans are key residues that facilitate the folding and stability of membrane proteins. Escherichia coli OmpX possesses two unique interface tryptophans, namely Trp76, which is present at the interface and is solvent-exposed, and Trp140, which is relatively more lipid solvated than Trp76 in symmetric lipid membranes. Here, we address the requirement for tryptophan and the consequences of aromatic amino acid substitutions on the folding and stability of OmpX. Using spectroscopic measurements of OmpX-Trp/Tyr/Phe mutants, we show that the specific mutation W76→Y allows barrel assembly >1...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29127738/concerted-millisecond-timescale-dynamics-in-the-intrinsically-disordered-carboxyl-terminus-of-%C3%AE-tubulin-induced-by-mutation-of-a-conserved-tyrosine-residue
#18
Jason Harris, Maria Shadrina, Carlos Oliver, Jackie Vogel, Anthony Mittermaier
Tubulins are an ancient family of eukaryotic proteins characterized by an amino-terminal globular domain and disordered carboxyl terminus. These carboxyl termini play important roles in modulating the behavior of microtubules in living cells. However, the atomic-level basis of their function is not well understood. These regions contain multiple acidic residues and their overall charges are modulated in vivo by post-translational modifications, e.g. phosphorylation. In this study, we describe an application of NMR and computer Monte Carlo simulations to investigate how the modification of local charge alters the conformational sampling of the γ-tubulin carboxyl terminus...
November 11, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29126486/functionalized-carbon-quantum-dots-with-dopamine-for-tyrosinase-activity-analysis
#19
Jin-Jie Hu, Xiao-Lin Bai, Yi-Ming Liu, Xun Liao
Tyrosinase (TYR) is a key enzyme in melanin biosynthesis and its activity is an important biomarker for dermatological disorders, such as vitiligo, melanoma and actinic damages. Sensitive assay for TYR activity is significant for basic and clinical research. In this work, a facile fluorescent assay for TYR activity based on dopamine functionalized carbon quantum dots (CQDs-Dopa) has been developed. Dopamine (Dopa) was covalently bond to CQDs through a simple one-pot hydrothermal method, and the prepared CQDs-Dopa exhibited a fluorescence emission at 499 nm under exciting wavelength at 310 nm with a quantum yield of approximately 2...
December 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29123501/gonadotropin-releasing-hormone-gnrh-receptor-structure-and-gnrh-binding
#20
REVIEW
Colleen A Flanagan, Ashmeetha Manilall
Gonadotropin-releasing hormone (GnRH) regulates reproduction. The human GnRH receptor lacks a cytoplasmic carboxy-terminal tail but has amino acid sequence motifs characteristic of rhodopsin-like, class A, G protein-coupled receptors (GPCRs). This review will consider how recent descriptions of X-ray crystallographic structures of GPCRs in inactive and active conformations may contribute to understanding GnRH receptor structure, mechanism of activation and ligand binding. The structures confirmed that ligands bind to variable extracellular surfaces, whereas the seven membrane-spanning α-helices convey the activation signal to the cytoplasmic receptor surface, which binds and activates heterotrimeric G proteins...
2017: Frontiers in Endocrinology
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