1. Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China 2. Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, China
In Lactococcus lactis, the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.
. [J]. Frontiers of Chemical Science and Engineering, 2019, 13(1): 133-139.
Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li. Molecular simulation of the interaction mechanism between CodY protein and DNA in Lactococcus lactis. Front. Chem. Sci. Eng., 2019, 13(1): 133-139.
JZhang, J Zhong. The journey of nisin development in China, a natural-green food preservative. Protein & Cell, 2015, 6(10): 709–711 https://doi.org/10.1007/s13238-015-0214-9
2
ASong, L In, SLim, R ARahim. A review on Lactococcus lactis: From food to factory. Microbial Cell Factories, 2017, 16(1): 55 https://doi.org/10.1186/s12934-017-0669-x
3
KPapadimitriou, A Alegria, P ABron, MAngelis, MGobbetti, MKleerebezem. Stress physiology of lactic acid bacteria. Microbiology and Molecular Biology Reviews, 2016, 80(3): 837–890 https://doi.org/10.1128/MMBR.00076-15
4
D JMcMahon, C J Oberg, M A Drake, N Farkye, L VMoyes, M RArnold, BGanesan, JSteele, J RBroadbent. Effect of sodium, potassium, magnesium, and calcium salt cations on pH, proteolysis, organic acids, and microbial populations during storage of full-fat cheddar cheese. Journal of Dairy Science, 2014, 97(8): 4780–4798 https://doi.org/10.3168/jds.2014-8071
5
VLaroute, C Yasaro, WNarin, RMazzoli, EPessione, PLoubiere. GABA production in Lactococcus lactis is enhanced by arginine and co-addition of malate. Frontiers in Microbiology, 2016, 7: 1050 https://doi.org/10.3389/fmicb.2016.01050
6
JDelcour, T Ferain, MDeghorain, EPalumbo, PHols. The biosynthesis and functionality of the cell-wall of lactic acid bacteria. Antonie van Leeuwenhoek, 1999, 76(1/4): 159–184 https://doi.org/10.1023/A:1002089722581
7
AHartke, S Bouche, J CGiard, ABenachour, PBoutibonnes, YAuffray. The lactic acid stress response of Lactococcus lactis subsp. lactis. Current Microbiology, 1996, 33(3): 194–199 https://doi.org/10.1007/s002849900099
8
B RBelitsky, A L Sonenshein. Genome-wide identification of Bacillus subtilis CodY-binding sites at single-nucleotide resolution. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(17): 7026–7031 https://doi.org/10.1073/pnas.1300428110
9
TYuan, Y K Guo, J K Dong, T Y Li, T Zhou, K WSun, MZhang, Q YWu, ZXie, Y Z Cai, et al.. Construction, characterization and application of a genome-wide promoter library in Saccharomyces cerevisiae. Frontiers of Chemical Science and Engineering, 2017, 11(1): 107–116 https://doi.org/10.1007/s11705-017-1621-7
10
V MLevdikov, E Blagova, V LYoung, B RBelitsky, ALebedev, A LSonenshein, A JWilkinson. Structure of the branched-chain amino acid and GTP-sensing global regulator, CodY, from Bacillus subtilis. Journal of Biological Chemistry, 2017, 292(7): 2714–2728 https://doi.org/10.1074/jbc.M116.754309
11
MBiasini, S Bienert, AWaterhouse, KArnold, GStuder, TSchmidt, FKlefer, T GCassarino, MBertonl, LBordoli, et al.. Swiss-model: Modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research, 2014, 42(W1): W252–W258 https://doi.org/10.1093/nar/gku340
12
D ACase, T A Darden, T E III Cheatham. AMBER 12. 2012
13
S AAdcock, J A Mccammon. Molecular dynamics: Survey of methods for simulating the activity of proteins. Chemical Reviews, 2006, 106(5): 1589–1615 https://doi.org/10.1021/cr040426m
14
UEssmann, L Perera, MBerkowitz, TDarden, HLee, L G Pedersen. A smooth particle mesh Ewald method. Journal of Chemical Physics, 1998, 103(19): 8577–8593 https://doi.org/10.1063/1.470117
15
CColovos, T O Yeates. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Science, 1993, 2(9): 1511–1519 https://doi.org/10.1002/pro.5560020916
16
MWiederstein, M J Slppl. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research, 2007, 35(Web Server): W407–W410 https://doi.org/10.1093/nar/gkm290
17
OErcan, M Wels, E JSmid, MKleerebezem. Molecular and metabolic adaptations of Lactococcus lactisat near-zero growth rates. Applied and Environmental Microbiology, 2015, 81(1): 320–331 https://doi.org/10.1128/AEM.02484-14
18
M VDijk, A M Bonvin. 3D-DART: A DNA structure modeling server. Nucleic Acids Research, 2009, 37(Web Server): W235–W239 https://doi.org/10.1093/nar/gkp287
19
M VDijk, A D Dijk, V Hsu, RBoelens, A MBonvin. Information-driven protein-DNA docking using HADDOCK: It is a matter of flexibility. Nucleic Acids Research, 2006, 34(11): 3317–3325 https://doi.org/10.1093/nar/gkl412
20
IMassova, P A Kollman. Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Perspectives in Drug Discovery and Design, 2000, 18(1): 113–135 https://doi.org/10.1023/A:1008763014207
21
JKottalam, D A Case. Langevin modes of macromolecules: Applications to crambin and DNA hexamers. Biopolymers, 1990, 29(10-11): 1409–1421 https://doi.org/10.1002/bip.360291008
22
K ASharp, B Honig. Electrostatic interactions in macromolecules: Theory and applications. Annual Review of Biophysics and Biophysical Chemistry, 1990, 19(1): 301–332 https://doi.org/10.1146/annurev.bb.19.060190.001505
23
DSitkoff, K A Sharp, B Honig. Accurate calculation of hydration free energies using macroscopic solvent models. Journal of Physical Chemistry, 1994, 98(7): 1978–1988 https://doi.org/10.1021/j100058a043
24
W CStill, A Tempczyk, R CHawley, THendirckson. Semianalytical treatment of solvation for molecular mechanics and dynamics. Journal of the American Chemical Society, 1990, 112(16): 6127–6129 https://doi.org/10.1021/ja00172a038
