8JY1
Structure of Mangifera Indica Epoxide hydrolase 2
Summary for 8JY1
| Entry DOI | 10.2210/pdb8jy1/pdb |
| Descriptor | Epoxide hydrolase-2, TETRAETHYLENE GLYCOL (3 entities in total) |
| Functional Keywords | alpha-beta hydrolase epoxide hydrolase, plant protein |
| Biological source | Mangifera indica (mango) |
| Total number of polymer chains | 2 |
| Total formula weight | 73601.71 |
| Authors | Bhoite, A.S.,Gupta, V.S.,Kulkarni, K.A. (deposition date: 2023-07-02, release date: 2024-08-07, Last modification date: 2026-02-25) |
| Primary citation | Bhoite, A.,Gaur, N.K.,Palang, M.,Kontham, R.,Gupta, V.,Kulkarni, K. Structure of epoxide hydrolase 2 from Mangifera indica throws light on the substrate specificity determinants of plant epoxide hydrolases Biochem.Biophys.Res.Commun., 733:150444-150444, 2024 Cited by PubMed Abstract: Epoxide hydrolases (EHs) are a group of ubiquitous enzymes that catalyze hydrolysis of chemically reactive epoxides to yield corresponding dihydrodiols. Despite extensive studies on EHs from different clades, generic rules governing their substrate specificity determinants have remained elusive. Here, we present structural, biochemical and molecular dynamics simulation studies on MiEH2, a plant epoxide hydrolase from Mangifera indica. Comparative structure-function analysis of nine homologs of MiEH2, which include a few AlphaFold structural models, show that the two conserved tyrosines (MiEH2 and MiEH2) from the lid domain dissect substrate binding tunnel into two halves, forming substrate-binding-pocket one (BP1) and two (BP2). This compartmentalization offers diverse binding modes to their substrates, as exemplified by the binding of smaller aromatic substrates, such as styrene oxide (SO). Docking and molecular dynamics simulations reveal that the linear epoxy fatty acid substrates predominantly occupy BP1, while the aromatic substrates can bind to either BP1 or BP2. Furthermore, SO preferentially binds to BP2, by stacking against catalytically important histidine (MiEH2) with the conserved lid tyrosines engaging its epoxide oxygen. Residue (MiEH2) next to the catalytic aspartate (MiEH2) modulates substrate binding modes. Thus, the divergent binding modes correlate with the differential affinities of the EHs for their substrates. Furthermore, long-range dynamical coupling between the lid and core domains critically influences substrate enantioselectivity in plant EHs. PubMed: 39067247DOI: 10.1016/j.bbrc.2024.150444 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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