Steroid-Protein Interactions II

Westphal, Ulrich

doi:10.1007/978-3-642-82486-9

Cited by 63 publications

(89 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In blood, SHBG exists as a homodimer (Westphal, 1986) and, although the crystallographic analysis allows for the observation of a single G domain, analysis of crystal packing reveals a plausible model for homodimer formation. In this model, the monomers are related by a 2-fold crystallographic symmetry axis parallel to the β-strands, and this places β-strand 7 of one monomer next to the β-strand 10 of the second monomer, and vice versa ( Figure 3A).…”

Section: Dimerization Of Shbgmentioning

confidence: 99%

“…It has been estimated that only a single steroid molecule is bound per SHBG homodimer (Westphal, 1986), and it has been proposed that this could be achieved by the formation of a single steroid-binding site by two monomeric units Sui et al, 1996). Other data have suggested that the steroid-binding sites of each monomer are located in close proximity to the dimerization Figure 2B.…”

Section: Dimerization Of Shbgmentioning

confidence: 99%

“…Human SHBG binds testosterone, its precursor androst-5-ene-3β,17β-diol and its biologically active 5α-reduced metabolites with approximately nanomolar affinities (Westphal, 1986). It also binds oestradiol with relatively high affinity, and in this regard differs from SHBG in many other mammalian species (Renoir et al, 1980).…”

Section: Determinants Of Human Shbg Steroid-binding Affinity and Specmentioning

confidence: 99%

“…Human sex hormone-binding globulin (SHBG, alternative name: sex steroid-binding protein, SBP) is a homodi-meric plasma glycoprotein that binds both androgens and oestradiol with nanomolar affinities (Siiteri et al, 1982;Westphal, 1986). Plasma SHBG is produced primarily in hepatocytes, and a differently glycosylated isoform (Cheng et al, 1985), androgen-binding protein (ABP), is produced in the Sertoli cells of the testis (French and Ritzen, 1973).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain

Grishkovskaya

Avvakumov

Sklenar

et al. 2000

EMBO J

153

141

View full text Add to dashboard Cite

Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and regulates their access to target tissues. In biological fluids, SHBG exists as a homodimer and each monomer comprises two laminin G-like domains (G domains). The crystal structure of the N-terminal G domain of SHBG in complex with 5α-dihydrotestosterone at 1.55 Å resolution reveals both the architecture of the steroid-binding site and the quaternary structure of the dimer. We also show that G domains have jellyroll topology and are structurally related to pentraxin. In each SHBG monomer, the steroid intercalates into a hydrophobic pocket within the β-sheet sandwich. The steroid and a 20 Å distant calcium ion are not located at the dimer interface. Instead, two separate steroid-binding pockets and calcium-binding sites exist per dimer. The structure displays intriguing disorder for loop segment Pro130-Arg135. In all other jellyroll proteins, this loop is well ordered. If modelled accordingly, it covers the steroidbinding site and could thereby regulate access of ligands to the binding pocket.

show abstract

Section: Dimerization Of Shbgmentioning

confidence: 99%

Section: Dimerization Of Shbgmentioning

confidence: 99%

Section: Determinants Of Human Shbg Steroid-binding Affinity and Specmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain

Grishkovskaya

Avvakumov

Sklenar

et al. 2000

EMBO J

153

141

View full text Add to dashboard Cite

show abstract

“…Plasma sex hormone-binding globulin (SHBG) binds testosterone and estradiol with high affinity, and selectively transports sex steroid hormones in human plasma (Westphal, 1986, Siiteri et al, 1982, Hammond, 1990. Circulating SHBG is a major determinant of the metabolic clearance of sex steroid hormones, and it modulates their access to target tissues.…”

Section: Introductionmentioning

confidence: 99%

Sex hormone-binding globulin gene expression in the liver: Drugs and the metabolic syndrome

Pugeat

Nader

Hogeveen

et al. 2010

Molecular and Cellular Endocrinology

108

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4α levels, a transcription factor that play a critical role in controlling the SHBG promoter. Interestingly, diminishing hepatic lipogenesis and free fatty acid liver biosynthesis also appear to be associated with the positive effects of thyroid hormones and PPARγ antagonists on SHBG expression. This mechanism provides a biological explanation for why SHBG is a sensitive biomarker of insulin resistance and the metabolic syndrome, and why low plasma SHBG levels are a risk factor for developing hyperglycemia and type 2 diabetes, especially in women. These important advances in our knowledge of the regulation of SHBG expression in the liver open new approaches for identifying and preventing metabolic disorder associated diseases early in life.

show abstract

Biological activities of the shrub Salsola tuberculatiformis Botsch.: Contraceptive or stress alleviator?

2003

View full text Add to dashboard Cite

Plants belonging to the genus Salsola (Family: Chenopodiaceae) are common in the arid and semiarid regions of our planet with no less than 69 different Salsola species found in Namibia and the Republic of South Africa. This genus is used as a traditional medicine and aqueous extracts of Salsola have been used by Bushmen women as an oral contraceptive. Ingestion of the Namibian shrub Salsola tuberculatiformis Botsch. by pregnant Karakul sheep leads to prolonged gestation and fetal post-maturity and, as a result, the pelts of the new-born karakul lambs are worthless. This initiated an investigation into the active agents in the plant, using the terminal enzyme in adrenal corticosteroidogenesis, cytochrome P450-dependent 11beta-hydroxylase (P450c11), as a bioassay. Although the active fraction, S2, was extremely labile, partial structure determination suggested the presence of synephrine and a highly reactive aziridine. Therefore a more stable analogue, 2-(4-acetoxyphenyl)2-chloro-N-methylethylammonium-chloride (compound A), was synthesised, which, like the active plant extracts, inhibited adrenal steroidogenesis and acted as a contraceptive. In addition, compound A was stabilised by interaction with steroid-binding globulins in plasma thus enhancing biological activity in vivo. These findings provided explanations for the complex biological effects of the shrub as well as a new insight into the mode of action of chemically labile plant products in vivo.

show abstract

Steroid-Protein Interactions II

Cited by 63 publications

References 0 publications

Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain

Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain

Sex hormone-binding globulin gene expression in the liver: Drugs and the metabolic syndrome

Biological activities of the shrub Salsola tuberculatiformis Botsch.: Contraceptive or stress alleviator?

Contact Info

Product

Resources

About