2003
DOI: 10.1074/jbc.m210135200
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Comparative Enzymology of 11β-Hydroxysteroid Dehydrogenase Type 1 from Glucocorticoid Resistant (Guinea Pig) Versus Sensitive (Human) Species

Abstract: Type 1 11␤-hydroxysteroid dehydrogenase constitutes a prereceptor control mechanism through its ability to reduce dehydroglucocorticoids to the receptor ligands cortisol and corticosterone in vivo. We compared kinetic characteristics of the human and guinea pig 11␤-hydroxysteroid dehydrogenase isozymes derived from species differing in glucocorticoid sensitivity. Both orthologs were successfully expressed as full-length enzymes in yeast and COS7 cells and as soluble transmembrane-deleted constructs in Escheric… Show more

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Cited by 28 publications
(20 citation statements)
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“…Each dimer, therefore, has one Tyr123 pointing into the active site and one Tyr123 pointing toward bulk solvent. Although this conformation is highly suggestive of cooperative kinetics for 11b-HSD1, 13 the data from this study and others [37][38][39] do not support this concept. The fact that the protein is not in its physiological environment could mean that the kinetics seen here and elsewhere are not indicative of the in-cell situation.…”
Section: Discussioncontrasting
confidence: 48%
“…Each dimer, therefore, has one Tyr123 pointing into the active site and one Tyr123 pointing toward bulk solvent. Although this conformation is highly suggestive of cooperative kinetics for 11b-HSD1, 13 the data from this study and others [37][38][39] do not support this concept. The fact that the protein is not in its physiological environment could mean that the kinetics seen here and elsewhere are not indicative of the in-cell situation.…”
Section: Discussioncontrasting
confidence: 48%
“…Purification of Guinea Pig 11␤-HSD1-N-terminally His 6 -tagged, transmembrane domain-deleted 11␤-HSD1 was expressed in the Escherichia coli expression strain BL21(DE3) as described previously (10). Optimization of protein production and purification conditions has been described in detail elsewhere (11).…”
Section: Methodsmentioning
confidence: 99%
“…Purification and thorough characterization of the membrane-attached 11␤-HSD isozymes have been difficult, and no structure determination has been reported yet. We recently described the successful expression and kinetic characterization of transmembrane domain-deleted human and guinea pig 11␤-HSD1 variants (10,11). We now present the successful crystallization and structure determination at 2.5 Å of the guinea pig enzyme and discuss the structural implications on enzyme function and membrane attachment.…”
mentioning
confidence: 99%
“…Subsequently, 11 -HSD1 cDNAs and proteins have been published for the human (Tannin et al 1991), mouse (Rajan et al 1995), squirrel monkey (Moore et al 1993), sheep (Yang et al 1992), rabbit (Ozols 1995), pig (Klemcke et al 2003), cow (Tetsuka et al 2003) and guinea-pig (Pu & Yang 2000, Shafqat et al 2003. Human liver 11 -HSD1 was purified in an active form and was postulated to exist as a dimer (Maser et al 2002).…”
Section: -Hydroxysteroid Dehydrogenase Type 1 (-Hsd1)mentioning
confidence: 99%