QM/MM study of the catalytic reaction of aphid myrosinase
(2024) In International Journal of Biological Macromolecules 262.- Abstract
Brevicoryne brassicae, an aphid species, exclusively consumes plants from the Brassicaceae family and employs a sophisticated defense mechanism involving a myrosinase enzyme that breaks down glucosinolates obtained from its host plants. In this work, we employed combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations to study the catalytic reaction of aphid myrosinase. A proper QM region to study the myrosinase reaction should contain the whole substrate, models of Gln-19, His-122, Asp-124, Asn-166, Glu-167, Lys-173, Tyr-180, Val-228, Tyr-309, Tyr-346, Ile-347, Glu-374, Glu-423, Trp-424, and a water molecule. The calculations show that Asp-124 and Glu-423 must be charged, His-122... (More)
Brevicoryne brassicae, an aphid species, exclusively consumes plants from the Brassicaceae family and employs a sophisticated defense mechanism involving a myrosinase enzyme that breaks down glucosinolates obtained from its host plants. In this work, we employed combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations to study the catalytic reaction of aphid myrosinase. A proper QM region to study the myrosinase reaction should contain the whole substrate, models of Gln-19, His-122, Asp-124, Asn-166, Glu-167, Lys-173, Tyr-180, Val-228, Tyr-309, Tyr-346, Ile-347, Glu-374, Glu-423, Trp-424, and a water molecule. The calculations show that Asp-124 and Glu-423 must be charged, His-122 must be protonated on NE2, and Glu-167 must be protonated on OE2. Our model reproduces the anomeric retaining characteristic of myrosinase and indicates that the deglycosylation reaction is the rate-determining step of the reaction. Based on the calculations, we propose a reaction mechanism for aphid myrosinase-mediated hydrolysis of glucosinolates with an overall barrier of 15.2 kcal/mol. According to the results, removing a proton from Arg-312 or altering it to valine or methionine increases glycosylation barriers but decreases the deglycosylation barrier.
(Less)
- author
- Jafari, Sonia ; Ryde, Ulf LU and Irani, Mehdi LU
- organization
- publishing date
- 2024-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- MD simulations, Mechanism, Myrosinase, QM/MM
- in
- International Journal of Biological Macromolecules
- volume
- 262
- article number
- 130089
- publisher
- Elsevier
- external identifiers
-
- pmid:38360236
- scopus:85185531221
- ISSN
- 0141-8130
- DOI
- 10.1016/j.ijbiomac.2024.130089
- language
- English
- LU publication?
- yes
- id
- 527ba0ee-7f0e-4c3e-b2aa-572b6b683431
- date added to LUP
- 2024-03-27 15:52:38
- date last changed
- 2024-04-24 19:52:30
@article{527ba0ee-7f0e-4c3e-b2aa-572b6b683431, abstract = {{<p>Brevicoryne brassicae, an aphid species, exclusively consumes plants from the Brassicaceae family and employs a sophisticated defense mechanism involving a myrosinase enzyme that breaks down glucosinolates obtained from its host plants. In this work, we employed combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations to study the catalytic reaction of aphid myrosinase. A proper QM region to study the myrosinase reaction should contain the whole substrate, models of Gln-19, His-122, Asp-124, Asn-166, Glu-167, Lys-173, Tyr-180, Val-228, Tyr-309, Tyr-346, Ile-347, Glu-374, Glu-423, Trp-424, and a water molecule. The calculations show that Asp-124 and Glu-423 must be charged, His-122 must be protonated on NE2, and Glu-167 must be protonated on OE2. Our model reproduces the anomeric retaining characteristic of myrosinase and indicates that the deglycosylation reaction is the rate-determining step of the reaction. Based on the calculations, we propose a reaction mechanism for aphid myrosinase-mediated hydrolysis of glucosinolates with an overall barrier of 15.2 kcal/mol. According to the results, removing a proton from Arg-312 or altering it to valine or methionine increases glycosylation barriers but decreases the deglycosylation barrier.</p>}}, author = {{Jafari, Sonia and Ryde, Ulf and Irani, Mehdi}}, issn = {{0141-8130}}, keywords = {{MD simulations; Mechanism; Myrosinase; QM/MM}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{International Journal of Biological Macromolecules}}, title = {{QM/MM study of the catalytic reaction of aphid myrosinase}}, url = {{http://dx.doi.org/10.1016/j.ijbiomac.2024.130089}}, doi = {{10.1016/j.ijbiomac.2024.130089}}, volume = {{262}}, year = {{2024}}, }