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Open AccessArticle

Structural Basis of Specific Glucoimidazole and Mannoimidazole Binding by Os3BGlu7

1
Center of Excellence in Computational Chemistry (CECC), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
2
School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
3
Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
4
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia
5
Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
6
Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand
*
Authors to whom correspondence should be addressed.
Present Address: Department of Biotechnology, Faculty of Agricultural Technology, Kalasin University, Kalasin 46000, Thailand
Biomolecules 2020, 10(6), 907; https://doi.org/10.3390/biom10060907
Received: 7 May 2020 / Revised: 9 June 2020 / Accepted: 11 June 2020 / Published: 15 June 2020
β-Glucosidases and β-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 β-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 −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 β-glycosidases. View Full-Text
Keywords: transition state mimics; β-glycosidase; X-ray crystallography; MD simulation; REMD transition state mimics; β-glycosidase; X-ray crystallography; MD simulation; REMD
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Nutho, B.; Pengthaisong, S.; Tankrathok, A.; Lee, V.S.; Ketudat Cairns, J.R.; Rungrotmongkol, T.; Hannongbua, S. Structural Basis of Specific Glucoimidazole and Mannoimidazole Binding by Os3BGlu7. Biomolecules 2020, 10, 907.

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