Structural Basis of Specific Glucoimidazole and Mannoimidazole Binding by Os3BGlu7
| Autor: | Bodee Nutho, S. Pengthaisong, Anupong Tankrathok, Thanyada Rungrotmongkol, James R. Ketudat Cairns, Supot Hannongbua, Vannajan Sanghiran Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Mannosidase Mannosides Protein Conformation Stereochemistry Binding energy lcsh:QR1-502 Molecular Dynamics Simulation Crystallography X-Ray 01 natural sciences Biochemistry Article lcsh:Microbiology Substrate Specificity 03 medical and health sciences Molecular dynamics 0103 physical sciences Amino Acid Sequence Glycosides β-glycosidase transition state mimics Molecular Biology 030304 developmental biology X-ray crystallography 0303 health sciences Binding Sites 010304 chemical physics biology Hydrogen bond Chemistry Hydrolysis beta-Glucosidase Imidazoles Active site Oryza MD simulation REMD Molecular Docking Simulation Glucose biology.protein Epimer Protein crystallization Mannose Protein Binding |
| Zdroj: | Biomolecules Volume 10 Issue 6 Biomolecules, Vol 10, Iss 907, p 907 (2020) |
| ISSN: | 2218-273X |
| DOI: | 10.3390/biom10060907 |
| Popis: | &beta Glucosidases and &beta mannosidases hydrolyze substrates that differ only in the epimer of the nonreducing terminal sugar moiety, but most such enzymes show a strong preference for one activity or the other. Rice Os3BGlu7 and Os7BGlu26 &beta glycosidases show a less strong preference, but Os3BGlu7 and Os7BGlu26 prefer glucosides and mannosides, respectively. Previous studies of crystal structures with glucoimidazole (GIm) and mannoimidazole (MIm) complexes and metadynamic simulations suggested that Os7BGlu26 hydrolyzes mannosides via the B2,5 transition state (TS) conformation preferred for mannosides and glucosides via their preferred 4H3/4E TS conformation. However, MIm is weakly bound by both enzymes. In the present study, we found that MIm was not bound in the active site of crystallized Os3BGlu7, but GIm was tightly bound in the &minus 1 subsite in a 4H3/4E conformation via hydrogen bonds with the surrounding residues. One-microsecond molecular dynamics simulations showed that GIm was stably bound in the Os3BGlu7 active site and the glycone-binding site with little distortion. In contrast, MIm initialized in the B2,5 conformation rapidly relaxed to a E3/4H3 conformation and moved out into a position in the entrance of the active site, where it bound more stably despite making fewer interactions. The lack of MIm binding in the glycone site in protein crystals and simulations implies that the energy required to distort MIm to the B2,5 conformation for optimal active site residue interactions is sufficient to offset the energy of those interactions in Os3BGlu7. This balance between distortion and binding energy may also provide a rationale for glucosidase versus mannosidase specificity in plant &beta glycosidases. |
| Databáze: | OpenAIRE |
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