| http://purl.uniprot.org/citations/12899831 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12899831 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12899831 | http://www.w3.org/2000/01/rdf-schema#comment | "Human 20alpha-hydroxysteroid dehydrogenase (h20alpha-HSD; AKR1C1) catalyzes the transformation of progesterone (Prog) into 20alpha-hydroxy-progesterone (20alpha-OHProg). Although h20alpha-HSD shares 98% sequence identity with human type 3 3alpha-HSD (h3alpha-HSD3, AKR1C2), these two enzymes differ greatly in their activities. In order to explain these differences, we have solved the crystal structure of h20alpha-HSD in a ternary complex with NADP(+) and 20alpha-OHProg at 1.59A resolution. The steroid is stabilized by numerous hydrophobic interactions and a hydrogen bond between its O20 and the N(epsilon ) atom of His222. This new interaction prevents the formation of a hydrogen bond with the cofactor, as seen in h3alpha-HSD3 ternary complexes. By combining structural, direct mutagenesis and kinetic studies, we found that the H(222)I substitution decreases the K(m) value for the cofactor 95-fold. With these results, we hypothesize that the rotation of the lateral chain of His222 could be a mediating step between the transformation of Prog and the release of the cofactor. Moreover, crystal structure analysis and direct mutagenesis experiments lead us to identify a new residue involved in the binding of Prog. Indeed, the R(304)L substitution leads to a 65-fold decrease in the K(m) value for Prog reduction. We thus propose that Prog is maintained in a new steroid-binding site composed mainly of residues found in the carboxy-terminal region of the protein."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.org/dc/terms/identifier | "doi:10.1016/s0022-2836(03)00762-9"xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.org/dc/terms/identifier | "doi:10.1016/s0022-2836(03)00762-9"xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Legrand P."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Legrand P."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Labrie F."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Labrie F."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Luu-The V."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Luu-The V."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Breton R."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Breton R."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Cantin L."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Cantin L."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Couture J.-F."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/author | "Couture J.-F."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/pages | "593-604"xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/pages | "593-604"xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/title | "Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids."xsd:string |
| http://purl.uniprot.org/citations/12899831 | http://purl.uniprot.org/core/title | "Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids."xsd:string |