TY - JOUR
T1 - Mutated form (G52E) of inactive diphtheria toxin CRM197
T2 - molecular simulations clearly display effect of the mutation to NAD binding
AU - Salmas, Ramin Ekhteiari
AU - Mestanoglu, Mert
AU - Unlu, Ayhan
AU - Yurtsever, Mine
AU - Durdagi, Serdar
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Mutated form (G52E) of diphtheria toxin (DT) CRM197 is an inactive and nontoxic enzyme. Here, we provided a molecular insight using comparative molecular dynamics (MD) simulations to clarify the influence of a single point mutation on overall protein and active-site loop. Post-processing MD analysis (i.e. stability, principal component analysis, hydrogen-bond occupancy, etc.) is carried out on both wild and mutated targets to investigate and to better understand the mechanistic differences of structural and dynamical properties on an atomic scale especially at nicotinamide adenine dinucleotide (NAD) binding site when a single mutation (G52E) happens at the DT. In addition, a docking simulation is performed for wild and mutated forms. The docking scoring analysis and docking poses results revealed that mutant form is not able to properly accommodate the NAD molecule.
AB - Mutated form (G52E) of diphtheria toxin (DT) CRM197 is an inactive and nontoxic enzyme. Here, we provided a molecular insight using comparative molecular dynamics (MD) simulations to clarify the influence of a single point mutation on overall protein and active-site loop. Post-processing MD analysis (i.e. stability, principal component analysis, hydrogen-bond occupancy, etc.) is carried out on both wild and mutated targets to investigate and to better understand the mechanistic differences of structural and dynamical properties on an atomic scale especially at nicotinamide adenine dinucleotide (NAD) binding site when a single mutation (G52E) happens at the DT. In addition, a docking simulation is performed for wild and mutated forms. The docking scoring analysis and docking poses results revealed that mutant form is not able to properly accommodate the NAD molecule.
KW - CRM197
KW - MD simulations
KW - binding interactions analysis
KW - diphtheria toxin
UR - http://www.scopus.com/inward/record.url?scp=84958538767&partnerID=8YFLogxK
U2 - 10.1080/07391102.2015.1119060
DO - 10.1080/07391102.2015.1119060
M3 - Article
C2 - 26836774
AN - SCOPUS:84958538767
SN - 0739-1102
VL - 34
SP - 2462
EP - 2468
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 11
ER -