scholarly journals Site-specific Binding Affinities within the H2B Tail Domain Indicate Specific Effects of Lysine Acetylation

2007 ◽  
Vol 282 (45) ◽  
pp. 32867-32876 ◽  
Author(s):  
Xiaodong Wang ◽  
Jeffrey J. Hayes
Keyword(s):  
Specific Binding ◽  
Lysine Acetylation ◽  
Binding Affinities ◽  
Tail Domain ◽  
Site Specific ◽  
Specific Effects

scholarly journals Site-specific effects of neurosteroids on GABAA receptor activation and desensitization

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yusuke Sugasawa ◽  
Wayland WL Cheng ◽  
John R Bracamontes ◽  
Zi-Wei Chen ◽  
Lei Wang ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Binding Sites ◽  
Specific Binding ◽  
Receptor Activation ◽  
Allosteric Modulation ◽  
Receptor Desensitization ◽  
Antagonist Activity ◽  
Competitive Antagonist ◽  
Site Specific ◽  
Specific Effects

This study examines how site-specific binding to three identified neurosteroid-binding sites in the α1β3 GABAA receptor (GABAAR) contributes to neurosteroid allosteric modulation. We found that the potentiating neurosteroid, allopregnanolone, but not its inhibitory 3β-epimer epi-allopregnanolone, binds to the canonical β3(+)–α1(-) intersubunit site that mediates receptor activation by neurosteroids. In contrast, both allopregnanolone and epi-allopregnanolone bind to intrasubunit sites in the β3 subunit, promoting receptor desensitization and the α1 subunit promoting effects that vary between neurosteroids. Two neurosteroid analogues with diazirine moieties replacing the 3-hydroxyl (KK148 and KK150) bind to all three sites, but do not potentiate GABAAR currents. KK148 is a desensitizing agent, whereas KK150 is devoid of allosteric activity. These compounds provide potential chemical scaffolds for neurosteroid antagonists. Collectively, these data show that differential occupancy and efficacy at three discrete neurosteroid-binding sites determine whether a neurosteroid has potentiating, inhibitory, or competitive antagonist activity on GABAARs.

scholarly journals Site-specific effects of neurosteroids on GABAA receptor activation and desensitization

2020 ◽  
Author(s):  
Yusuke Sugasawa ◽  
Wayland W. L. Cheng ◽  
John R. Bracamontes ◽  
Zi-Wei Chen ◽  
Lei Wang ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Binding Sites ◽  
Specific Binding ◽  
Receptor Activation ◽  
Allosteric Modulation ◽  
Receptor Desensitization ◽  
Antagonist Activity ◽  
Competitive Antagonist ◽  
Site Specific ◽  
Specific Effects

ABSTRACTThis study examines how site-specific binding to the three identified neurosteroid binding sites in the α1β3 GABAA receptor (GABAAR) contributes to neurosteroid allosteric modulation. We found that the potentiating neurosteroid, allopregnanolone, but not its inhibitory 3β-epimer epi-allopregnanolone, binds to the canonical β3(+)–α1(-) intersubunit site that mediates receptor activation by neurosteroids. In contrast, both allopregnanolone and epi-allopregnanolone bind to intrasubunit sites in the β3 subunit, promoting receptor desensitization and the α1 subunit promoting ligand-specific effects. Two neurosteroid analogues with diazirine moieties replacing the 3-hydroxyl (KK148 and KK150) bind to all three sites, but do not potentiate GABAAR currents. KK148 is a desensitizing agent, whereas KK150 is devoid of allosteric activity. These compounds provide potential chemical scaffolds for site-specific and general neurosteroid antagonists. Collectively, these data show that differential occupancy and efficacy at three discrete neurosteroid binding sites determine whether a neurosteroid has potentiating, inhibitory, or competitive antagonist activity on GABAARs.

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

Obtaining Site-Specific Calcium-Binding Affinities Of Calmodulin

2003 ◽  
Vol 10 (4) ◽  
pp. 331-345 ◽  
Author(s):  
Jenny Yang ◽  
Amy Gawthrop ◽  
Yiming Ye
Keyword(s):  
Calcium Binding ◽  
Binding Affinities ◽  
Site Specific

scholarly journals Evaluating Mechanisms of IDH1 Regulation through Site-Specific Acetylation Mimics

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 740
Author(s):  
Joi Weeks ◽  
Alexandra I. Strom ◽  
Vinnie Widjaja ◽  
Sati Alexander ◽  
Dahra K. Pucher ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Translational Regulation ◽  
Catalytic Efficiency ◽  
Low Grade ◽  
Lysine Acetylation ◽  
Site Specific ◽  
Idh1 Mutations ◽  
Mutant Idh1 ◽  
Biochemical Features ◽  
Secondary Glioblastomas

Isocitrate dehydrogenase (IDH1) catalyzes the reversible NADP+-dependent oxidation of isocitrate to α-ketoglutarate (αKG). IDH1 mutations, primarily R132H, drive > 80% of low-grade gliomas and secondary glioblastomas and facilitate the NADPH-dependent reduction of αKG to the oncometabolite D-2-hydroxyglutarate (D2HG). While the biochemical features of human WT and mutant IDH1 catalysis have been well-established, considerably less is known about mechanisms of regulation. Proteomics studies have identified lysine acetylation in WT IDH1, indicating post-translational regulation. Here, we generated lysine to glutamine acetylation mimic mutants in IDH1 to evaluate the effects on activity. We show that mimicking lysine acetylation decreased the catalytic efficiency of WT IDH1, with less severe catalytic consequences for R132H IDH1.

scholarly journals Site-Specific Binding of Non-Site-Specific Ions

2019 ◽  
Vol 116 (12) ◽  
pp. 2237-2239 ◽  
Author(s):  
Shi-Jie Chen
Keyword(s):  
Specific Binding ◽  
Site Specific

Site-Specific Identification of Lysine Acetylation Stoichiometries in Mammalian Cells

2016 ◽  
Vol 15 (3) ◽  
pp. 1103-1113 ◽  
Author(s):  
Tong Zhou ◽  
Ying-hua Chung ◽  
Jianji Chen ◽  
Yue Chen
Keyword(s):  
Mammalian Cells ◽  
Lysine Acetylation ◽  
Site Specific ◽  
Specific Identification

scholarly journals Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53.

1992 ◽  
Vol 6 (10) ◽  
pp. 1886-1898 ◽  
Author(s):  
J Bargonetti ◽  
I Reynisdottir ◽  
P N Friedman ◽  
C Prives
Keyword(s):  
Specific Binding ◽  
T Antigen ◽  
Mutant P53 ◽  
Wild Type ◽  
Sv40 T Antigen ◽  
Site Specific ◽  
Wild Type P53 ◽  
Cellular Dna
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