Journal Article

Structure-Based Computational Study of Two Disease Resistance Gene Homologues (Hm1 and Hm2) in Maize (Zea mays L.) with Implications in Plant-Pathogen Interactions

Sahu, Jagajjit, Modi, Mahendra Kumar, Barooah, Madhumita, Sen, Priyabrata, Patra, Mahesh Chandra, Dehury, Budheswar, Maharana, Jitendra, Choudhury, Manabendra Dutta

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Agricultural biotechnology / Agriculture / Amino Acid Sequence / Ascomycota - metabolism / Ascomycota - physiology / Binding energy / Biodegradation / Bioinformatics / Biology and Life Sciences / CCR1 protein / Cereal crops / Computational chemistry / Computer applications / Computer simulation / Corn / Crop diseases / Crystallography / Decomposition / Disease resistance / Disease Resistance - genetics / Electrostatic properties / Enzymes / Free energy / Fungi / Genes / Genomics / Homology / Host-Pathogen Interactions / Hydrogen / Hydrogen bonds / Hydrophobicity / Kinases / Laboratories / Life sciences / Ligands / Mathematical analysis / Molecular docking / Molecular Docking Simulation / Molecular dynamics / Molecular Dynamics Simulation / Molecular Sequence Data / NADP / NADP - metabolism / Oxidoreductases - chemistry / Oxidoreductases - genetics / Oxidoreductases - metabolism / Peptides, Cyclic - metabolism / Physical Sciences / Plant diseases / Plant Diseases - microbiology / Plant Proteins - chemistry / Plant Proteins - genetics / Plant Proteins - metabolism / Proteins / Recognition / Reductases / Sequence Alignment / Sequence Homology, Nucleic Acid / Signal transduction / Thermodynamics / Toxins / Zea mays / Zea mays - genetics / Zea mays - immunology / Zea mays - microbiology