7C83
Crystal structure of an integral membrane steroid 5-alpha-reductase PbSRD5A
Summary for 7C83
| Entry DOI | 10.2210/pdb7c83/pdb |
| Descriptor | 3-oxo-5-alpha-steroid 4-dehydrogenase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total) |
| Functional Keywords | steroid reductase, nadph, steroid 3-oxo-delta(4) reduction, oxidoreductase |
| Biological source | Proteobacteria bacterium |
| Total number of polymer chains | 1 |
| Total formula weight | 32656.51 |
| Authors | Ren, R.B.,Han, Y.F.,Xiao, Q.J.,Deng, D. (deposition date: 2020-05-28, release date: 2021-01-27, Last modification date: 2024-04-03) |
| Primary citation | Han, Y.,Zhuang, Q.,Sun, B.,Lv, W.,Wang, S.,Xiao, Q.,Pang, B.,Zhou, Y.,Wang, F.,Chi, P.,Wang, Q.,Li, Z.,Zhu, L.,Li, F.,Deng, D.,Chiang, Y.C.,Li, Z.,Ren, R. Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism. Nat Commun, 12:449-449, 2021 Cited by PubMed Abstract: Steroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-Δ structure, such as testosterone or progesterone, are catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which are essential for multiple physiological and pathological processes. SRD5A2 is already a target of clinically relevant drugs. However, the detailed mechanism of SRD5A-mediated reduction remains elusive. Here we report the crystal structure of PbSRD5A from Proteobacteria bacterium, a homolog of both SRD5A1 and SRD5A2, in complex with the cofactor NADPH at 2.0 Å resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic substrate binding cavity, whereas TM5-7 coordinate cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and -2, together with biochemical characterization, define the substrate binding pocket of SRD5As, explain the properties of disease-related mutants and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-Δ reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible. PubMed: 33469028DOI: 10.1038/s41467-020-20675-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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