| Autor: |
Mishra VK; Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. mishra@chem.iitkgp.ac.in., Mishra S; Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. mishra@chem.iitkgp.ac.in. |
| Jazyk: |
angličtina |
| Zdroj: |
Physical chemistry chemical physics : PCCP [Phys Chem Chem Phys] 2020 Jul 22; Vol. 22 (28), pp. 16013-16022. |
| DOI: |
10.1039/d0cp02351e |
| Abstrakt: |
Lipoxygenases are non-heme iron containing enzymes that catalyze oxygenation of poly-unsaturated fatty acids in different animal and plant species with extremely high regio- and stereospecificity. Nature employs 8-lipoxygenase to produce 8R-hydroperoxide from the oxygenation of arachidonic acid. A single-point L434F mutation of 8-lipoxygenase alters the regio- and stereospecificity of the final products, with a product ratio of 66 : 34 for 8R- and 12S-hydroperoxide, respectively. A molecular level explanation of this flipped regiospecificity is presented in this work on the basis of molecular dynamics simulations and transition network analysis of oxygen migration in the protein matrix. Phe434 is shown to exist in two conformations, the so-called open and closed conformations. In the closed conformation, the phenyl group of Phe434 shields the C8 site of the substrate, thereby preventing access of the oxygen molecule to this site, which leads to a quenching of the 8R-product. On the other hand, both closed and open conformations of Phe434 allow the oxygen molecule to approach the pro-S face of the C12 site of the substrate, which enhances the propensity of the 12S-hydroperoxide. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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