Molecular Modeling Clarifies the Mechanism of Chromophore Maturation in the Green Fluorescent Protein

Тип документаJournal Article
Дата публикации2017-08-02
Название журналаJournal of the American Chemical Society
ИздательAmerican Chemical Society
КвартильQ1
ISSN00027863, 15205126
  • General Chemistry
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry
Краткое описание
We report the first complete theoretical description of the chain of elementary reactions resulting in chromophore maturation in the green fluorescent protein (GFP). All reaction steps including cyclization, dehydration, and oxidation are characterized at the uniform quantum mechanics/molecular mechanics (QM/MM) computational level using density functional theory in quantum subsystems. Starting from a structure of the wild-type protein with the noncyclized Ser65-Tyr66-Gly67 tripeptide, we modeled cyclization and dehydration reactions. We then added molecular oxygen to the system and modeled the oxidation reaction resulting in the mature protein-bound chromophore. Computationally derived structures of the reaction product and several reaction intermediates agree well with the relevant crystal structures, validating the computational protocol. The highest computed energy barriers at the cyclization-dehydration (17 kcal/mol) and oxidation (21 kcal/mol) steps agree well with the values derived from the kinetics measurements (20.7 and 22.7 kcal/mol, respectively). The simulations provide strong support to the mechanism involving the cyclization-dehydration-oxidation sequence of the chromophore's maturation reactions. The results also establish a solid basis for predictions of maturation mechanisms in other fluorescent proteins.
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1. Grigorenko B.L., Krylov A.I., Nemukhin A.V. Molecular Modeling Clarifies the Mechanism of Chromophore Maturation in the Green Fluorescent Protein // Journal of the American Chemical Society. 2017. Т. 139. № 30. С. 10239–10249.
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TY - JOUR

DO - 10.1021/jacs.7b00676

UR - http://dx.doi.org/10.1021/jacs.7b00676

TI - Molecular Modeling Clarifies the Mechanism of Chromophore Maturation in the Green Fluorescent Protein

T2 - Journal of the American Chemical Society

AU - Grigorenko, Bella L.

AU - Krylov, Anna I.

AU - Nemukhin, Alexander V.

PY - 2017

DA - 2017/07/19

PB - American Chemical Society (ACS)

SP - 10239-10249

IS - 30

VL - 139

SN - 0002-7863

SN - 1520-5126

ER -

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@article{2017,

doi = {10.1021/jacs.7b00676},

url = {https://doi.org/10.1021%2Fjacs.7b00676},

year = 2017,

month = {jul},

publisher = {American Chemical Society ({ACS})},

volume = {139},

number = {30},

pages = {10239--10249},

author = {Bella L. Grigorenko and Anna I. Krylov and Alexander V. Nemukhin},

title = {Molecular Modeling Clarifies the Mechanism of Chromophore Maturation in the Green Fluorescent Protein}

}

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Grigorenko, Bella L., Anna I. Krylov, and Alexander V. Nemukhin. “Molecular Modeling Clarifies the Mechanism of Chromophore Maturation in the Green Fluorescent Protein.” Journal of the American Chemical Society 139.30 (2017): 10239–10249. Crossref. Web.