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Catalytic diversity and homotropic allostery of two Cytochrome P450 monooxygenase like proteins from Trichoderma brevicompactum

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Abstract

Trichothecenes are the secondary metabolites produced by Trichoderma spp. Some of these molecules have been reported for their ability to stimulate plant growth by suppressing plant diseases and hence enabling Trichoderma spp. to be efficiently used as biocontrol agents in modern agriculture. Many of the proteins involved in the trichothecenes biosynthetic pathway in Trichoderma spp. are encoded by the genes present in the tri cluster. Tri4 protein catalyzes three consecutive oxygenation reaction steps during biosynthesis of isotrichodiol in the trichothecenes biosynthetic pathway, while tri11 protein catalyzes the C4 hydroxylation of 12, 13-epoxytrichothec-9-ene to produce trichodermol. In the present study, we have homology modelled the three-dimensional structures of tri4 and tri11 proteins. Furthermore, molecular dynamics simulations were carried out to elucidate the mechanism of their action. Both tri4 and tri11 encode for cytochrome P450 monooxygenase like proteins. These data also revealed effector-induced allosteric changes on substrate binding at an alternative binding site and showed potential homotropic negative cooperativity. These analyses also showed that their catalytic mechanism relies on protein–ligand and protein–heme interactions controlled by hydrophobic and hydrogen-bonding interactions which orient the complex in optimal conformation within the active sites.

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Abbreviations

MD:

Molecular dynamics

TDN:

Trichodiene

EPT:

12, 13-epoxytrichothec-9-ene

SMs:

Secondary metabolites

SRSs:

Substrate recognition sites

P450s:

Cytochrome P450 monooxygenases

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Acknowledgements

We acknowledge Central University of Himachal Pradesh and Bioinformatics Resources and Applications Facility, Centre for Development in Advanced Computing, Pune for providing the computational infrastructure. RH acknowledges National Fellowship for Higher Education from University Grants Commission, Govt. of India (UGC). SS receives research stipend from UGC. Research in YA lab is supported by extramural research funds from UGC, Science and Engineering Research Board (DST, Govt. of India), and Indian Council of Medical Research. We thank Dr. P. Aparoy for his generous help during the revision. Prof. Claudio Luchinat (editor-in-chief) and two anonymous referees are also sincerely acknowledged, whose insightful comments and advice during the editorial review helped us to improve our work enormously.

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Authors and Affiliations

  1. Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India

    Razak Hussain & Tabreiz Ahmad Khan

  2. Department of Environmental Science, School of Earth and Environmental Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Kangra, Himachal Pradesh, 176206, India

    Indu Kumari, Shikha Sharma & Mushtaq Ahmed

  3. Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Kangra, Himachal Pradesh, 176206, India

    Yusuf Akhter

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  1. Razak Hussain
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  2. Indu Kumari
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Correspondence to Yusuf Akhter.

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Hussain, R., Kumari, I., Sharma, S. et al. Catalytic diversity and homotropic allostery of two Cytochrome P450 monooxygenase like proteins from Trichoderma brevicompactum . J Biol Inorg Chem 22, 1197–1209 (2017). https://doi.org/10.1007/s00775-017-1496-6

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  • DOI: https://doi.org/10.1007/s00775-017-1496-6

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