Structural highlights
Function
HDHA_CLOSR 7alpha-hydroxysteroid dehydrogenase that catalyzes the NADP(+)-dependent oxidation of the 7alpha-hydroxy group of 7alpha-hydroxysteroids, such as cholate, chenodeoxycholate, glycochenodeoxycholate and taurochenodeoxycholate, to the corresponding 7-oxosteroids (PubMed:22198717, PubMed:24810359). Is also able to catalyze the reverse reduction reactions (PubMed:22198717). Together with 7beta-HSDH encoded in the adjacent gene, is likely involved in the epimerization of the hydroxy group at C-7 of primary bile acids through 7-keto bile acid intermediates (PubMed:22198717).[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ferrandi EE, Bertolesi GM, Polentini F, Negri A, Riva S, Monti D. In search of sustainable chemical processes: cloning, recombinant expression, and Appl Microbiol Biotechnol. 2012 Sep;95(5):1221-33. PMID:22198717 doi:10.1007/s00253-011-3798-x
- ↑ Lou D, Wang B, Tan J, Zhu L. Carboxyl-terminal and Arg38 are essential for activity of the 7α-hydroxysteroid dehydrogenase from Clostridium absonum. Protein Pept Lett. 2014;21(9):894-900. PMID:24810359 doi:10.2174/0929866521666140507160050
- ↑ Lou D, Wang B, Tan J, Zhu L, Cen X, Ji Q, Wang Y. The three-dimensional structure of Clostridium absonum 7alpha-hydroxysteroid dehydrogenase: new insights into the conserved arginines for NADP(H) recognition. Sci Rep. 2016 Mar 10;6:22885. doi: 10.1038/srep22885. PMID:26961171 doi:http://dx.doi.org/10.1038/srep22885
