8GK3
Cytochrome P450 3A7 in complex with Dehydroepiandrosterone sulfate
Summary for 8GK3
| Entry DOI | 10.2210/pdb8gk3/pdb |
| Descriptor | Cytochrome P450 3A7, PROTOPORPHYRIN IX CONTAINING FE, 17-oxoandrost-5-en-3beta-yl hydrogen sulfate, ... (4 entities in total) |
| Functional Keywords | monooxygenase, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 12 |
| Total formula weight | 680805.44 |
| Authors | Liu, J.,Scott, E.E. (deposition date: 2023-03-16, release date: 2023-07-26, Last modification date: 2023-08-30) |
| Primary citation | Liu, J.,Kandel, S.E.,Lampe, J.N.,Scott, E.E. Human cytochrome P450 3A7 binding four copies of its native substrate dehydroepiandrosterone 3-sulfate. J.Biol.Chem., 299:104993-104993, 2023 Cited by PubMed Abstract: Human fetal cytochrome P450 3A7 (CYP3A7) is involved in both xenobiotic metabolism and the estriol biosynthetic pathway. Although much is understood about cytochrome P450 3A4 and its role in adult drug metabolism, CYP3A7 is poorly characterized in terms of its interactions with both categories of substrates. Herein, a crystallizable mutated form of CYP3A7 was saturated with its primary endogenous substrate dehydroepiandrosterone 3-sulfate (DHEA-S) to yield a 2.6 Å X-ray structure revealing the unexpected capacity to simultaneously bind four copies of DHEA-S. Two DHEA-S molecules are located in the active site proper, one in a ligand access channel, and one on the hydrophobic F'-G' surface normally embedded in the membrane. While neither DHEA-S binding nor metabolism exhibit cooperative kinetics, the current structure is consistent with cooperativity common to CYP3A enzymes. Overall, this information suggests that mechanism(s) of CYP3A7 interactions with steroidal substrates are complex. PubMed: 37392852DOI: 10.1016/j.jbc.2023.104993 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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