Maturation of GFPFluorescent ProteinsAcetylcholinesteraseAspartoacylase

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

 


Author: Bella L. Grigorenko, Anna I. Krylov, Alexander V. Nemukhin
Publication: Journal of American Chemical Society
DOI: 10.1021/jacs.7b00676
Cite as: J. Am. Chem. Soc. 139, 30, 10239-10249


 

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.

Copyright © 2017, American Chemical Society

Photoinduced Chemistry in Fluorescent Proteins: Curse or Blessing?


Author: Atanu Acharya, Alexey M. Bogdanov, Bella L. Grigorenko, Ksenia B. Bravaya, Alexander V. Nemukhin, Konstantin A. Lukyanov, Anna I. Krylov
Publication: Chemical Reviews
DOI: 10.1021/acs.chemrev.6b00238
Cite as: Chem. Rev. 117, 2, 758-795


 

Photoinduced reactions play an important role in the photocycle of fluorescent proteins from the green fluorescent protein (GFP) family. Among such processes are photoisomerization, photooxidation/photoreduction, breaking and making of covalent bonds, and excited-state proton transfer (ESPT). Many of these transformations are initiated by electron transfer (ET). The quantum yields of these processes vary significantly, from nearly 1 for ESPT to 10–4 – 10–6  for ET. Importantly, even when quantum yields are relatively small, at the conditions of repeated illumination the overall effect is significant.

Copyright © 2017, American Chemical Society

Understanding the non-catalytic behavior of human butyrylcholinesterase silent variants: Comparison of wild-type enzyme, catalytically active Ala328Cys mutant, and silent Ala328Asp variant


Author: Sofya Lushchekina, Alexander Nemukhin, Sergei Varfolomeev, Patrick Masson
Publication: Chemico-Biological Interactions
DOI: 10.1016/j.cbi.2016.04.007
Cite as: Chem.-Biol. Interact. 259 (B), 223-232


Conformational dynamics of wild-type human butyrylcholinesterase (BChE), two mutants of residue Ala328, the catalytically active Ala328Cys, and the catalytically inactive (silent) Ala328Asp, and their interactions with butyrylcholine were studied. The aim was to understand the molecular mechanisms by which point mutations may lead to silent BChE variant or alter catalytic activity. Importance of BChE natural variants is due to medical consequences, i.e. prolonged apnea, following administration of the myorelaxant esters, succinylcholine and mivacurium.

Copyright © 2016, Elsevier BV

Three Faces of N-Acetylaspartate: Activator, Substrate, and Inhibitor of Human Aspartoacylase


Author: Maria G. Khrenova, Ekaterina D. Kots, Sergey D. Varfolomeev, Sofya V. Lushchekina, Alexander V. Nemukhin
Publication: Journal of Physical Chemistry B
DOI: 10.1021/acs.jpcb.7b08759
Cite as: J. Phys. Chem. B 121, 40, 9389-9397


 

Hydrolysis of N-acetylaspartate (NAA), one of the most concentrated metabolites in brain, catalyzed by human aspartoacylase (hAsp) shows a remarkable dependence of the reaction rate on substrate concentration. At low NAA concentrations, sigmoidal shape of kinetic curve is observed, followed by typical rate growth of the enzyme-catalyzed reaction, whereas at high NAA concentrations self-inhibition takes place. We show that this rate dependence is consistent with a molecular model, in which N-acetylaspartate appears to have three faces in the enzyme reaction, acting as activator at low concentrations, substrate at moderate concentrations, and inhibitor at high concentrations.

Copyright © 2017, American Chemical Society