Estradiol induces allosteric coupling and partitioning of sex-hormone-binding globulin monomers among conformational states

Jasuja, Ravi; Spencer, Daniel J.; Jayaraj, Abhilash; Peng, Liming; Krishna, Meenakshi; Lawney, Brian; Patel, Priyank Pravin; Jayaram, B.; Thayer, Kelly M.; Beveridge, David L.; Bhasin, Shalender

doi:10.1016/j.isci.2021.102414

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…Traditionally, allosteric signals are considered to be "one-way-trips," where perturbations stemming from allosteric sites leverage variations towards the corresponding orthosteric sites, thereby conferring regulatory impacts. 9,29,117,[129][130][131][132] However, with the crosstalk between allosteric and orthosteric sites becomes more and more thoroughly characterized, a novel bidirectional allosteric signaling theory was put forward. In this theory, regulatory signals can not only originate from allosteric sites and head towards orthosteric sites, but also can transduce reversely from orthosteric sites towards allosteric sites.…”

Section: Allosteric Signal Analysismentioning

confidence: 99%

“…Traditionally, allosteric signals are considered to be “one‐way‐trips,” where perturbations stemming from allosteric sites leverage variations towards the corresponding orthosteric sites, thereby conferring regulatory impacts 9,29,117,129–132 . However, with the crosstalk between allosteric and orthosteric sites becomes more and more thoroughly characterized, a novel bidirectional allosteric signaling theory was put forward.…”

Section: Allosteric Signal Analysismentioning

confidence: 99%

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Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Chai

Wang

et al. 2021

WIREs Comput Mol Sci

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Allostery is a universal, biological phenomenon in which orthosteric sites are finetuned by topologically distal allosteric sites triggered by perturbations, such as ligand binding, residue mutations, or post-translational modifications. Allosteric regulation is implicated in a variety of physiological and pathological conditions and is thus emerging as a novel avenue for drug discovery. Allosteric drugs have traditionally been discovered by serendipity through large-scale experimental screening. Recently, we have witnessed significant progress in biophysics, particularly in structural bioinformatics, which has facilitated the in-depth characterization of allosteric effects and the accurate detection of allosteric residues and exosites. These advances improve our understanding of allosterism and promote allosteric drug discovery, thereby revolutionizing the shift from the traditional serendipitous route used to discover allosteric drugs to the updated path centered on rational structure-based design. In this review, recent advances in computational methods applied to allosteric drug discovery are summarized. We comprehensively review these achievements along various levels of allosteric events, from the construction of allosteric databases to the identification and analysis of allosteric residues, signals, sites, and modulators. We expect to increase the awareness of the discovery of allosteric drugs using structure-based computational methods.

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Section: Allosteric Signal Analysismentioning

confidence: 99%

Section: Allosteric Signal Analysismentioning

confidence: 99%

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Chai

Wang

et al. 2021

WIREs Comput Mol Sci

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“…As measurement of free sex steroid hormone concentration are complex and time-consuming, calculation of free sex steroid hormones, using measured total E2/total T and SHBG in conjunction with equilibrium-binding theory or empirical equations became popular, regardless of their unreliability [ 44 , 45 ]. Equilibrium-binding equation-based calculation methods presented to be even worse than assumption-free empirical formulae [ 44 , 46 ], as the SHBG as well as the albumin association constant for E2/T differs up to 14-fold between different authors [ 16 , 47 , 48 ]. Therefore, results based on the calculated free androgen index should be considered with caution.…”

Section: Discussionmentioning

confidence: 99%

Association of sex steroid hormones and new bone formation rate after iliac onlay grafting: a prospective clinical pilot study

et al. 2022

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Purpose The present prospective study evaluates the association between new bone formation rate in the iliac onlay graft and sex steroid hormone serum levels. Methods A total of 15 partially or completely edentulous postmenopausal females and 9 males with less than 5 mm height of the remaining alveolar bone underwent iliac onlay grafting followed by dental implant placement using a two-stage approach. Sex hormone binding globulin and 17β-estradiol serum levels were investigated by electrochemiluminescence immunoassay, while total testosterone level was analyzed using radioimmunoassay. At the time of implant placement, 12 weeks after grafting, bone biopsies were obtained and analyzed histomorphometrically. Statistical analysis was performed using linear mixed models. Results Grafting procedure was successfully performed in all patients. The mean new bone formation rate was 32.5% (116 samples). In men the mean new bone formation rate (38.1%) was significantly higher (p < 0.01) than in women (27.6%). Independent of gender 17β-estradiol and testosterone were positively associated to overall new bone formation rate, albeit a significant influence was only seen for 17β-estradiol in men (p = 0.020). Sex hormone binding globulin had no influence on new bone formation rate (p = 0.897). There was no significant association between new bone formation rate and age (p = 0.353) or new bone formation rate and body mass index (p = 0.248). Conclusion Positive association of 17ß-estradiol as well as testosterone with new bone formation rate after iliac onlay grafting indicates a role of sex steroid hormones in alveolar bone regeneration, although the observed influence was only significant for 17ß-estradiol in men. Graphical Abstract

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“…FT concentrations in human serum samples were determined using a standardized protocol of equilibrium dialysis coupled with LC‐MS/MS assay for testosterone. Equilibrium dialysis was performed in 96‐well plates (Harvard Apparatus, Holliston, MA) with semi‐permeable membranes that allow species less than 10 kDa to pass through 41,43 . The dialysis buffer composition simulated the ionic strength conditions of the human plasma: 90 mM NaCl, 3 nM KCl, 1.3 mM KH2PO4, 1.9 mM, 1.1 mM MgSO 4 ·7H 2 O, 5 mM 0.30 g urea and 23 mM HEPES sodium salt, 30 nM HEPES acid, 8 mM sodium azide, and 1 ml of 0.06% DL lactic acid.…”

Section: Methodsmentioning

confidence: 99%

“…Equilibrium dialysis was performed in 96-well plates (Harvard Apparatus, Holliston, MA) with semi-permeable membranes that allow species less than 10 kDa to pass through. 41,43 The dialysis buffer composition simulated the ionic strength conditions of the human plasma: 90 mM NaCl, 3 nM KCl, 1.3 mM KH2PO4, 1.9 mM, 1.1 mM MgSO 4 ⋅7H 2 O, 5 mM 0.30 g urea and 23 mM HEPES sodium salt, 30 nM HEPES acid, 8 mM sodium azide, and 1 ml of 0.06% DL lactic acid. Note that 200 µl of dialysis buffer was added to the "buffer side," and 200 µl of undiluted serum was added to the "sample side.…”

Section: A Standardized Equilibrium Dialysis Procedures Coupled With ...mentioning

confidence: 99%

Reference intervals for free testosterone in adult men measured using a standardized equilibrium dialysis procedure

et al. 2022

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Background: Free testosterone (FT) determination may be helpful in evaluating men suspected of testosterone deficiency especially in conditions with altered bindingprotein concentrations. However, methods for measuring FT by equilibrium dialysis and reference intervals vary among laboratories.Objective: To determine reference intervals for FT in healthy, nonobese men by age groups as well as in healthy young men, 19-39 years, using a standardized equilibrium dialysis procedure Methods: We measured FT in 145 healthy, nonobese men, 19 years or older, using a standardized equilibrium dialysis method performed for 16-h at 37 • C using undiluted serum and dialysis buffer that mimicked the ionic composition of human plasma. FT in dialysate was measured using a CDC-certified liquid chromatography tandem mass spectrometry assay.

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Estradiol induces allosteric coupling and partitioning of sex-hormone-binding globulin monomers among conformational states

Cited by 13 publications

References 41 publications

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Association of sex steroid hormones and new bone formation rate after iliac onlay grafting: a prospective clinical pilot study

Reference intervals for free testosterone in adult men measured using a standardized equilibrium dialysis procedure

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