Predicted Unfolding Order of the 13 α-Helices in the Catalytic Domain of Glucoamylase from Aspergillus awamori var. X100 by Molecular Dynamics Simulations

2003 ◽  
Vol 19 (5) ◽  
pp. 1583-1590 ◽  
Author(s):  
H.-L. Liu ◽  
W.-C. Wang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Catalytic Domain ◽  
Aspergillus Awamori ◽  
Dynamics Simulations

Molecular Dynamics Simulations on the Complexes of Glucoamylase II (471) from Aspergillus awamori var. X100 with 1-Deoxynojirimycin and Lentiginosine

1997 ◽  
Vol 3 (7) ◽  
pp. 249-260 ◽  
Author(s):  
Francesca Cardona ◽  
Andrea Goti ◽  
Alberto Brandi ◽  
Maria Scarselli ◽  
Neri Niccolai ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Aspergillus Awamori ◽  
Dynamics Simulations

scholarly journals Molecular Mechanism of Light-Induced Acceleration of the Adenosine Triphosphate Conversion to the Cyclic Adenosine Monophosphate Catalyzed by the Photoactivated Adenylyl Cyclase bPAC

2020 ◽  
Author(s):  
Alexander Nemukhin ◽  
Maria Khrenova ◽  
Anna M. Kulakova
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Adenylyl Cyclase ◽  
Adenosine Triphosphate ◽  
Catalytic Domain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Bluf Domain ◽  
Dynamics Simulations ◽  
Photoactivated Adenylyl Cyclase

<p>We report the first computational characterization of an optogenetic system composed of two photosensing BLUF (<u>b</u>lue <u>l</u>ight sensor <u>u</u>sing <u>f</u>lavin adenine dinucleotide) domains and two catalytic adenylyl cyclase (AC) domains. Conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi) catalyzed by ACs coupled with excitation in photosensing domains has emerged in the focus of modern optogenetic applications because of the request in photoregulated enzymes to modulate cellular concentrations of signaling messengers. The photoactivated adenylyl cyclase from the soil bacterium <i>Beggiatoa sp.</i> (bPAC) is an important model showing considerable increase of the ATP to cAMP conversion rate in the catalytic domain after the illumination of the BLUF domain. The 1 μs classical molecular dynamics simulations reveal that the activation of the BLUF domain leading to tautomerization of Gln49 in the chromophore binding pocket results in switching of position of the side chain of Arg278 in the active site of AC. Allosteric signal transmission pathways between Gln49 from BLUF and Arg278 from AC were revealed by the dynamical network analysis. The Gibbs energy profiles of the ATP → cAMP + PPi reaction computed using QM(DFT(ωB97X-D3/6-31G**))/MM(CHARMM) molecular dynamics simulations for both Arg278 conformations in AC clarify the reaction mechanism. In the light-activated system, the corresponding arginine conformation stabilizes the pentacoordinated phosphorus of the α-phosphate group in the transition state, thus lowering the activation energy. Simulations of the bPAC system with the Tyr7Phe replacement in BLUF demonstrate occurrence of both arginine conformations in an equal ratio, explaining the experimentally observed intermediate catalytic activity of the bPAC-Y7F variant as compared with the dark and light states of the wild type bPAC. </p>

scholarly journals Molecular Mechanism of Light-Induced Acceleration of the Adenosine Triphosphate Conversion to the Cyclic Adenosine Monophosphate Catalyzed by the Photoactivated Adenylyl Cyclase bPAC

2020 ◽  
Author(s):  
Alexander Nemukhin ◽  
Maria Khrenova ◽  
Anna M. Kulakova
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Adenylyl Cyclase ◽  
Adenosine Triphosphate ◽  
Catalytic Domain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Bluf Domain ◽  
Dynamics Simulations ◽  
Photoactivated Adenylyl Cyclase

<p>We report the first computational characterization of an optogenetic system composed of two photosensing BLUF (<u>b</u>lue <u>l</u>ight sensor <u>u</u>sing <u>f</u>lavin adenine dinucleotide) domains and two catalytic adenylyl cyclase (AC) domains. Conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi) catalyzed by ACs coupled with excitation in photosensing domains has emerged in the focus of modern optogenetic applications because of the request in photoregulated enzymes to modulate cellular concentrations of signaling messengers. The photoactivated adenylyl cyclase from the soil bacterium <i>Beggiatoa sp.</i> (bPAC) is an important model showing considerable increase of the ATP to cAMP conversion rate in the catalytic domain after the illumination of the BLUF domain. The 1 μs classical molecular dynamics simulations reveal that the activation of the BLUF domain leading to tautomerization of Gln49 in the chromophore binding pocket results in switching of position of the side chain of Arg278 in the active site of AC. Allosteric signal transmission pathways between Gln49 from BLUF and Arg278 from AC were revealed by the dynamical network analysis. The Gibbs energy profiles of the ATP → cAMP + PPi reaction computed using QM(DFT(ωB97X-D3/6-31G**))/MM(CHARMM) molecular dynamics simulations for both Arg278 conformations in AC clarify the reaction mechanism. In the light-activated system, the corresponding arginine conformation stabilizes the pentacoordinated phosphorus of the α-phosphate group in the transition state, thus lowering the activation energy. Simulations of the bPAC system with the Tyr7Phe replacement in BLUF demonstrate occurrence of both arginine conformations in an equal ratio, explaining the experimentally observed intermediate catalytic activity of the bPAC-Y7F variant as compared with the dark and light states of the wild type bPAC. </p>

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