Abstract
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.
Highlights
Plant diseases can considerably decline the net crop yields and the crop quality by releasing toxins that affect human health, as the outcome of disease outbreak is getting severe across the globe
HCTR2 (360 amino acids) consists of five domains, namely short chain dehydrogenase (Val5-Gly139), Epimerase (Val7- Ala275), NmrA (Val7-His125), 3Beta_HSD (Cys8 -Ser267) and NAD binding 4 domain (Val9 to His259). These cl09931 superfamily of proteins are comprised of Rossmann-fold NAD(P)(+) binding proteins sharing a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain, found in numerous dehydrogenases and redox enzymes with a vital role in several metabolic pathways and detoxification processes
We have modeled and predicted the interaction between the cofactor, NADPH and two disease resistance enzymes, HCTR1 and HCTR2 of maize plant using molecular docking and molecular dynamics (MD) simulations
Summary
Plant diseases can considerably decline the net crop yields and the crop quality by releasing toxins that affect human health, as the outcome of disease outbreak is getting severe across the globe. The host plant initiates transcription of the defense response (DR) gene, including the pathogenesis-related (PR) gene that confers local or systemic resistance [4,5]. Because of selective pressure from multitude of pathogens, plants have evolved post invasion mechanisms, which are controlled by dominant resistance genes that detects specific pathogen effector molecules (for example, Avirulence molecule (Avr)) through direct or indirect means and initiates active defense response. The R-gene mediated resistance is fundamentally racespecific which is only effective against pathogen strains expressing the cognate effector recognised by the R protein. This mechanism is frequently associated with hypersensitive response (HR), resulting in death of the infected cells, known as gene-forgene (R-Avr) interaction
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