3P3L
Crystal Structure of the Cytochrome P450 monooxygenase AurH (wildtype) from Streptomyces Thioluteus
Summary for 3P3L
| Entry DOI | 10.2210/pdb3p3l/pdb |
| Related | 3P3L 3P3O 3P3X 3P3Z |
| Descriptor | Cytochrome P450, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (6 entities in total) |
| Functional Keywords | cytochrome p450, monooxygenase, oxidoreductase |
| Biological source | Streptomyces thioluteus |
| Total number of polymer chains | 2 |
| Total formula weight | 92179.40 |
| Authors | Zocher, G.,Richter, M.E.A.,Mueller, U.,Hertweck, C. (deposition date: 2010-10-05, release date: 2011-02-16, Last modification date: 2024-02-21) |
| Primary citation | Zocher, G.,Richter, M.E.,Mueller, U.,Hertweck, C. Structural fine-tuning of a multifunctional cytochrome p450 monooxygenase. J.Am.Chem.Soc., 133:2292-2302, 2011 Cited by PubMed Abstract: AurH is a unique cytochrome P450 monooxygenase catalyzing the stepwise formation of a homochiral oxygen heterocycle, a key structural and pharmacophoric component of the antibiotic aureothin. The exceptional enzymatic reaction involves a tandem oxygenation process including a regio- and stereospecific hydroxylation, followed by heterocyclization. For the structural and biochemical basis of this unparalleled sequence, four crystal structures of AurH variants in different conformational states and in complex with the P450 inhibitor ancymidol were solved, which represent the first structures of the CYP151A group. Structural data in conjunction with computational docking, site-directed mutagenesis, and chemical analyses unveiled a switch function when recognizing the two substrates, deoxyaureothin and the hydroxylated intermediate, thus allowing the second oxygenation-heterocyclization step. Furthermore, we were able to modify the chemo- and regioselectivity of AurH, yielding mutants that catalyze the regioselective six-electron transfer of a nonactivated methyl group to a carboxylic acid via hydroxyl and aldehyde intermediates. PubMed: 21280577DOI: 10.1021/ja110146z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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