Genetic analysis of 11β-hydroxysteroid dehydrogenase

White, Perrin C.; Obeid, Jihad S.; Agarwal, Anik K.; Tannin, Grace M.; Nikkila, Heli

doi:10.1016/0039-128x(94)90086-8

Cited by 18 publications

(15 citation statements)

References 30 publications

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“…The tissue distribution of 11 -HSD2 has been ascertained by RNA blot hybridisation in human tissues, and the enzyme is expressed in high amounts in adult mineralocorticoid target tissues (Edwards et al 1988), such as kidney (Agarwal et al 1994, Albiston et al 1994 and colon (Whorwood et al 1994). Immunohistochemistry (Krozowski et al 1995) and in situ hybridisation studies localised 11 -HSD2 in the kidney to the renal collecting ducts in the cortex, most of the medulla, the connecting tubule and the distal convoluted tubule.…”

Section: -Hsd2 Localisationmentioning

confidence: 99%

“…However, no mutations were identified in the four unrelated AME patients whose gene was first sequenced (White et al 1994). With the discovery of the 11 -HSD2 isozyme and the elucidation of its gene structure, the focus for determining the causative mutation for AME moved to 11 -HSD2.…”

Section: Molecular Basis For Amementioning

confidence: 99%

“…This sequence has been implicated as part of the enzyme active site in some members of the short-chain dehydrogenase family (Persson et al 1991). Mutagenesis studies of Tyr-179 and Lys-183 have shown these residues to be essential for enzymatic activity of 11 -HSD1 (White et al 1994). Mutation of the serine residues within the YSASK region of rat 11 -HSD1 has indicated that these residues play an important role in determining the rate of the catalytic reaction (Obeyesekere et al 1998).…”

Section: Structural Analysis Of 11 -Hsd1mentioning

confidence: 99%

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11β-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action

Draper¹,

Stewart²

2005

Journal of Endocrinology

347

294

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Section: -Hsd2 Localisationmentioning

confidence: 99%

Section: Molecular Basis For Amementioning

confidence: 99%

Section: Structural Analysis Of 11 -Hsd1mentioning

confidence: 99%

See 1 more Smart Citation

11β-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action

Draper¹,

Stewart²

2005

Journal of Endocrinology

347

294

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“…ture of CsgA is observed in segment aF that contains amino acids forming a portion of the catalytic motif YXXXK (Ensor andTai 1991, 1994;Albalat et al 1992;Obeid and White 1992;Chen et al 1993;White et al 1994). CsgA has an AY repeat in this domain (Fig.…”

Section: Csga Mutations That Abolish Developmentmentioning

confidence: 99%

A tactile sensory system of Myxococcus xanthus involves an extracellular NAD(P)(+)-containing protein.

Lee¹,

Lee²,

Méndez³

et al. 1995

Genes Dev.

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CsgA is a cell surface protein that plays an essential role in tactile responses during Myxococcus xanthus fruiting body formation by producing the morphogenic C-signal. The primary amino acid sequence of CsgA exhibits homology with members of the short-chain alcohol dehydrogenase (SCAD) family and several lines of evidence suggest that NAD(P)+ binding is essential for biological activity. First, the predicted CsgA secondary structure based on the 3a120P-hydroxysteroid dehydrogenase crystal structure suggests that the amino-terminal portion of the protein contains an NAD(P)+ binding pocket. Second, strains with csgA alleles encoding amino acid substitutions T6A and RlOA in the NAD(P)+ binding pocket failed to develop. Third, exogenous MalE-CsgA rescues csgA development, whereas MalE-CsgA with the amino acid substitution CsgA T6A does not. Finally, csgA spore yield increased -20% when buffer containing 100 nM of MalE-CsgA was supplemented with 10 p~ of NAD+ or NADP+. Conversely, 10 p~ of NADH or NADPH delayed development for -24 hr and depressed spore levels -10%. Together, these results argue that NAD(P)' binding is critical for C-signaling. S135 and K155 are conserved amino acids in the catalytic domain of SCAD members. Strains with csgA alleles encoding the amino acid substitutions S135T or K155R failed to develop. Furthermore, a MalE-CsgA protein containing CsgA S135T was not able to restore development to csgA cells. In conclusion, a&ino acids conserved in the coenzyme binding pocket and catalytic site are essential for C-signaling.

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“…The defect is characterized by increased half-lives for cortisol, retention of sodium (despite low mineralocorticoid FIG. 4 (92). The molecular basis for the deficiency has been elucidated after the isolation of the gene for type II 11␤-HSD, which is the human kidneyspecific isoform (76).…”

Section: ␤-Hsd Deficiencymentioning

confidence: 99%