Fosfomycin induced structural change in fosfomycin resistance kinases FomA: molecular dynamics and molecular docking studies.
Fosfomycin resistance kinases FomA, one of the key enzymes responsible for bacterial resistances to fosfomycin, has gained much attention recently due to the raising public concern for multi-drug resistant bacteria. Using molecular docking followed by molecular dynamics simulations, our group illustrated the process of fosfomycin induced conformational change of FomA. The detailed roles of the catalytic residues (Lys18, His58 and Thr210) during the formation of the enzyme-substrate complex were shown in our research. The organization functions of Gly53, Gly54, Ile61 and Leu75 were also highlighted. Furthermore, the cation-π interaction between Arg62 and Trp207 was observed and speculated to play an auxiliary role in the conformation change process of the enzyme. This detailed molecular level illustration of the formation of FomA·ATP·Mg·Fosfomycin complex could provide insight for both anti-biotic discovery and improvement of fosfomycin in the future.
State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, Jilin, P R China.
Yun-Jian
YJ
Wu
Qing-Chuan
QC
Zheng
Ji-Long
JL
Zhang
Wen-Ting
WT
Chu
Ying-Lu
YL
Cui
Yan
Y
Wang
Hong-Xing
HX
Zhang
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D024901:Drug Resistance, Multiple, Bacterial; D005578:Fosfomycin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008024:Ligands; D005578:Fosfomycin; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D008274:Magnesium