JBIC Journal of Biological Inorganic Chemistry

, Volume 22, Issue 8, pp 1197–1209 | Cite as

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

  • Razak Hussain
  • Indu Kumari
  • Shikha Sharma
  • Mushtaq Ahmed
  • Tabreiz Ahmad Khan
  • Yusuf Akhter
Original Paper

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.

Keywords

Trichoderma brevicompactum Cytochrome P450 monooxygenase Trichodiene 12, 13-epoxytrichothec-9-ene Homotropic cooperativity 

Abbreviations

MD

Molecular dynamics

TDN

Trichodiene

EPT

12, 13-epoxytrichothec-9-ene

SMs

Secondary metabolites

SRSs

Substrate recognition sites

P450s

Cytochrome P450 monooxygenases

Notes

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.

Supplementary material

775_2017_1496_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1874 kb)

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Copyright information

© SBIC 2017

Authors and Affiliations

  1. 1.Department of BotanyAligarh Muslim UniversityAligarhIndia
  2. 2.Department of Environmental Science, School of Earth and Environmental SciencesCentral University of Himachal PradeshKangraIndia
  3. 3.Centre for Computational Biology and Bioinformatics, School of Life SciencesCentral University of Himachal PradeshKangraIndia

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