Exploring the molecular basis for selective binding of homoserine dehydrogenase from Mycobacterium leprae TN toward inhibitors: a virtual screening study.
Homoserine dehydrogenase (HSD) from Mycobacterium leprae TN is an antifungal target for antifungal properties including efficacy against the human pathogen. The 3D structure of HSD has been firmly established by homology modeling methods. Using the template, homoserine dehydrogenase from Thiobacillus denitrificans (PDB Id 3MTJ), a sequence identity of 40% was found and molecular dynamics simulation was used to optimize a reliable structure. The substrate and co-factor-binding regions in HSD were identified. In order to determine the important residues of the substrate (L-aspartate semialdehyde (L-ASA)) binding, the ASA was docked to the protein; Thr163, Asp198, and Glu192 may be important because they form a hydrogen bond with HSD through AutoDock 4.2 software. neuraminidaseAfter use of a virtual screening technique of HSD, the four top-scoring docking hits all seemed to cation-π ion pair with the key recognition residue Lys107, and Lys207. These ligands therefore seemed to be new chemotypes for HSD. Our results may be helpful for further experimental investigations.
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China. zdlgale@126.com.
Dongling
D
Zhan
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China. gykfamily@163.com.
Dongmei
D
Wang
College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China. minwh2000@163.com.
Weihong
W
Min
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China. weiweihan@jlu.edu.cn.
Weiwei
W
Han
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006715:Homoserine Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000201:enzymology*; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D012372:ROC Curve; D015203:Reproducibility of Results; D016415:Sequence Alignment; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D009243:NAD; D001224:Aspartic Acid; C006644:aspartic semialdehyde; D006715:Homoserine Dehydrogenase