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Publication Abstract from PubMed

7alpha-hydroxysteroid dehydrogenase (7alpha-HSDH) can catalyse the oxidation of C7 alpha-OH of the steroid nucleus in the bile acid metabolism. In the paper we determined the crystal structure of 7alpha-HSDH from Clostridium absonum (CA 7alpha-HSDH) complexed with taurochenodeoxycholic acid (TCDCA) and NADP(+) by X-ray diffraction, which, as a tetramer, possesses the typical alpha/beta folding pattern. The four subunits of an asymmetric unit lie in the fact that there are the stable hydrophobic interactions between Q-axis-related subunits. Significantly, we captured an active state of the NADP(+), confirming that nicotinamide moiety of NADP(+) act as electron carrier in the dehydrogenation. On the basis of crystal structure analysis, site-directed mutagenesis and MD simulation, furthermore, we find that the guanidinium of Arg38 can form the stable cation-pi interaction with the adenine ring of NADP(+), and the cation-pi interaction and hydrogen bonds between Arg38 and NADP(+) have a significant anchor effect on the cofactor binding to CA 7alpha-HSDH.

The three-dimensional structure of Clostridium absonum 7alpha-hydroxysteroid dehydrogenase: new insights into the conserved arginines for NADP(H) recognition.,Lou D, Wang B, Tan J, Zhu L, Cen X, Ji Q, Wang Y Sci Rep. 2016 Mar 10;6:22885. doi: 10.1038/srep22885. PMID:26961171^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.