3-alpha-HSD
I worked on 3-alpha-HSD as a postdoc in Mitchell Lewis' lab at the University of Pennsylvania, in collaboration with Trevor Penning's group. This enzyme is a HydroxySteroid Dehydrogenase, hence the abbreviation.
Rat liver 3-alpha-HSD inactivates circulating steroid hormones and is
involved in polycyclic aromatic hydrocarbon carcinogenesis. It is the only HSD
of known structure in the aldo-keto reductase superfamily and may provide a
paradigm for other mammalian HSDs in this family. The structure of the
apoenzyme was determined in 1994 at 3.2 Å resolution by Susan Hoog in Mitch's lab.
My project had two parts:
- 1. Structure of 3-alpha-HSD complexed with NADP at 2.7 Å resolution.
- 2. Structure of 3-alpha-HSD complexed with the competitive inhibitor testosterone.
HSD Publications
"Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP bound to 3-alpha-hydroxysteroid/dihydrodiol dehydrogenase", M.J. Bennett, R.H. Albert, J.M. Jez, H. Ma, T.M. Penning and M. Lewis (1997), Structure 5, p. 799-812.
"Comparative anatomy of the aldo-keto reductase superfamily", J. M. Jez, M.J. Bennett, B. P. Schlegel, M. Lewis and T. M. Penning (1997). Biochem. J. 326, p.625-636.
"Structure and Function of 3-alpha-hydroxysteroid dehydrogenase", T. M. Penning, M.J. Bennett, S.S. Hoog, B.P. Schlegel, J.M. Jez and M. Lewis (1997). Steroids 62, p. 101-111.
"The structure of 3-alpha-HSD complexed with NADP", M.J. Bennett, B.P. Schlegel, J.M. Jez, T.M. Penning and M. Lewis (1996), Biochemistry 35, p. 10702-10711.
"Mammalian 3-alpha-hydroxysteroid dehydrogenases", T.M. Penning, J.E. Pawlowski, B.P. Schlegel, J.M. Jez, H-K. Lin, S.S. Hoog, M.J. Bennett and M. Lewis (1996). Steroids 61, p. 508-523.
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