Conformational analysis of steroid hormone molecules in the lipid environment – A solid-state NMR approach

Shih, Ping-Chen; Li, Guo-Chian; Yang, Kai-Jay; Chen, Wenlung; Tzou, Der‐Lii M.

doi:10.1016/j.steroids.2011.02.005

Cited by 8 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, these methyl carbons behaved as unprotonated carbons. This phenomenon has been reported for other steroids [26,27]. Here we demonstrated that the selective detection of non-protonated and protonated signals in 13 C allowed us to assign the 13 C resonances of DHEA/Ca +2 mixtures.…”

Section: Mg +2 Revealing Different Spectral Patternsupporting

confidence: 82%

“…The resulting high-resolution 13 C CP/MAS NMR spectra are displayed in Fig. 1a, which is slightly different from the DHEA/lipid mixture that was previously reported [26]. A general spectral feature of these 13 C NMR spectra is that less than 10% of the 13 C resonances are distributed in a downfield zone (60-230 ppm), and more than 90% of the 13 C resonances are localized within an upfield zone (10-55 ppm).…”

Section: Chemical Shift Assignments Of Dheamentioning

confidence: 59%

“…Cross-polarization [23]/magic angle spinning [24] (CP/MAS) 13 C NMR solid-state spectroscopy techniques provide high-resolution spectra comparable to those observed in the solution phase, such that conformational information can be directly accessed. In fact, high-resolution { 1 H} 13 C CP/MAS spectra have been obtained from a variety of steroids, including testosterone, hydrocortisone, trans-dehydroandrosterone (DHEA), spironolac- tone, vitamin D and other steroids, such as deflazacort and prednisolone tert-butylacetate, revealing conformation flexibility by multiplet patterns with splittings of 0.2-2.1 ppm, which are indicative of various steroid conformations [25,26]. In addition, solid-state NMR has been applied to 17a-estradiol (E2a), 17b-estradiol (E2), and, E2 and E2a mixed with 1,2-dimyristoyl-sn-glycero-3-phosphocholine/ 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DMPC/DHPC) to probe steroidal ring conformations in a mimic lipid membrane environment [26,27].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, high-resolution { 1 H} 13 C CP/MAS spectra have been obtained from a variety of steroids, including testosterone, hydrocortisone, trans-dehydroandrosterone (DHEA), spironolac- tone, vitamin D and other steroids, such as deflazacort and prednisolone tert-butylacetate, revealing conformation flexibility by multiplet patterns with splittings of 0.2-2.1 ppm, which are indicative of various steroid conformations [25,26]. In addition, solid-state NMR has been applied to 17a-estradiol (E2a), 17b-estradiol (E2), and, E2 and E2a mixed with 1,2-dimyristoyl-sn-glycero-3-phosphocholine/ 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DMPC/DHPC) to probe steroidal ring conformations in a mimic lipid membrane environment [26,27]. The 13 C signals of the E2a/lipid spectrum revealed exclusively doublet patterns, whereas the 13 C signals of the E2/lipid spectrum revealed multiplet patterns, including doublet, triplet, or quartet.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cation ion specifically induces a conformational change in trans-dehydroandrosterone – A solid-state NMR study

et al. 2015

Self Cite

View full text Add to dashboard Cite

Section: Mg +2 Revealing Different Spectral Patternsupporting

confidence: 82%

Section: Chemical Shift Assignments Of Dheamentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cation ion specifically induces a conformational change in trans-dehydroandrosterone – A solid-state NMR study

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…LPS-lipid A was extracted routinely according to previously established protocols ( 24 , 59 , 60 ). First, bacterial cultures grown on LBA plates with an appropriate level of colistin were stripped and washed with washing buffer containing 30 mM Tris-HCl.…”

Section: Methodsmentioning

confidence: 99%

An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance

Wei

Lei

et al. 2018

mBio

131

View full text Add to dashboard Cite

Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin) conferred by Neisseria eptA, the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE). The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, etc.), rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and phosphoethanolamine [PEA] transferase) are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens.

show abstract

Solid‐state nuclear magnetic resonance investigation of neurosteroid compounds and magnesium interactions

Carillo

Tsai

et al. 2019

J Chinese Chemical Soc

View full text Add to dashboard Cite

The neurosteroid trans‐dehydroandrosterone (DHEA) and its analogs with slightly different modifications in the side chain attached to C17, that is, (3S)‐acetoxypregn‐5‐en‐20‐one (1) and (3S,20R)‐acetoxypregn‐5‐en‐20‐ol (2), have been synthesized to investigate DHEA–cation interactions. In this study, we applied solid‐state 1H/13C cross‐polarization/magic‐angle spinning (CP/MAS) nuclear magnetic resonance (NMR) spectroscopy to a series of DHEA analog/Mg2+ mixtures at different Mg2+ concentrations. The high‐resolution 13C NMR spectra of 1/Mg2+ mixtures exhibit two distinct 13C spectral patterns, one attributable to 1 free from Mg2+, and the other attributable to 1 with bound Mg2+. For 2, the 13C NMR spectra exhibit three distinct spectral patterns; besides that of the free form, the other two can be assigned to Mg2+‐bound forms. Based on the analysis of the chemical shift deviations (CSDs), we conclude that both 1 and 2 might be subject to a cation–π interaction via the C5–C6 double bond, in contrast to that observed previously for DHEA. As demonstrated, DHEA possesses two Mg2+ binding sites, that is, C17–O and C5–C6 double bond, in which the binding affinity of the former is at least three times stronger than that of the latter. The solid‐state 13C NMR investigation allows better understanding of the underlying cation binding effects of neurosteroid molecules in vitro.

show abstract

Conformational analysis of steroid hormone molecules in the lipid environment – A solid-state NMR approach

Cited by 8 publications

References 33 publications

Cation ion specifically induces a conformational change in trans-dehydroandrosterone – A solid-state NMR study

Cation ion specifically induces a conformational change in trans-dehydroandrosterone – A solid-state NMR study

An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance

Solid‐state nuclear magnetic resonance investigation of neurosteroid compounds and magnesium interactions

Contact Info

Product

Resources

About