Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep22885
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Funding
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2014ZX09301306-007]
- Program for Innovation Team Building at Institutions of Higher Education in Chongqing [KJTD201325]
- Basic and Frontier Research Project of Chongqin [cstc2015jcyjA10094]
- Visiting Scholar Foundation of the Key Laboratory of Biorheological Science and Technology (Chongqing University)
- Ministry of Education [CQKLBST-2012-007]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
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7 alpha-hydroxysteroid dehydrogenase (7 alpha-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 7 alpha-HSDH from Clostridium absonum (CA 7 alpha-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-axisrelated 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 7 alpha-HSDH.
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