Structure-based computational study of two disease resistance gene homologues (Hm1 and Hm2) in maize (Zea mays L.) with implications in plant-pathogen interactions.
The NADPH-dependent HC-toxin reductases (HCTR1 and 2) encoded by enzymatic class of disease resistance homologous genes (Hm1 and Hm2) protect maize by detoxifying a cyclic tetrapeptide, HC-toxin, secreted by the fungus Cochliobolus carbonum race 1(CCR1). Unlike the other classes' resistance (R) genes, HCTR-mediated disease resistance is an inimitable mechanism where the avirulence (Avr) component from CCR1 is not involved in toxin degradation. In this study, we attempted to decipher cofactor (NADPH) recognition and mode of HC-toxin binding to HCTRs through molecular docking, molecular dynamics (MD) simulations and binding free energy calculation methods. The rationality and the stability of docked complexes were validated by 30-ns MD simulation. The binding free energy decomposition of enzyme-cofactor complex was calculated to find the driving force behind cofactor recognition. The overall binding free energies of HCTR1-NADPH and HCTR2-NADPH were found to be -616.989 and -16.9749 kJ mol-1 respectively. The binding free energy decomposition revealed that the binding of NADPH to the HCTR1 is mainly governed by van der Waals and nonpolar interactions, whereas electrostatic terms play dominant role in stabilizing the binding mode between HCTR2 and NADPH. Further, docking analysis of HC-toxin with HCTR-NADPH complexes showed a distinct mode of binding and the complexes were stabilized by a strong network of hydrogen bond and hydrophobic interactions. This study is the first in silico attempt to unravel the biophysical and biochemical basis of cofactor recognition in enzymatic class of R genes in cereal crop maize.
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam, India; Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
Budheswar
B
Dehury
BIF-Centre, Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, Odisha, India; Animal Genomics Laboratory, Animal Biotechnology Centre, National Dairy Research Institute, Karnal, Haryana, India.
Mahesh Chandra
MC
Patra
BIF-Centre, Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, Odisha, India; Biotechnology Laboratory, Central Inland Fisheries Research Institute, Barrackpore, Kolkata, West Bengal, India.
Jitendra
J
Maharana
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam, India.
Jagajjit
J
Sahu
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam, India.
Priyabrata
P
Sen
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam, India.
Mahendra Kumar
MK
Modi
Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
Manabendra Dutta
MD
Choudhury
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam, India.
Madhumita
M
Barooah
D000595:Amino Acid Sequence; D001203:Ascomycota / Q000378:metabolism / Q000502:physiology; D060467:Disease Resistance / Q000235:genetics; D054884:Host-Pathogen Interactions; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D010935:Plant Diseases / Q000382:microbiology*; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013816:Thermodynamics; D003313:Zea mays / Q000235:genetics* / Q000276:immunology / Q000382:microbiology
D010456:Peptides, Cyclic; D010940:Plant Proteins; D009249:NADP; C037654:HC toxin; C078135:HC toxin reductase, Zea mays; D010088:Oxidoreductases