Journal ArticleDOI
Proteomic Atomics Reveals a Distinctive Uracil-5-Methyltransferase
Subrata Pramanik,Manisha Thaker,Ananda Gopu Perumal,Rajasekaran Ekambaram,Naresh Poondla,Markus Schmidt,Pok Son Kim,Arne Kutzner,Klaus Heese +8 more
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TLDR
This atomic‐based proteome map provides a unique approach for the identification of parasite‐specific proteins that could be considered as novel therapeutic targets for the treatment of malaria.Abstract:
Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in >1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria. Around 300 million clinical cases of malaria occur each year in tropical and subtropical regions of the world, resulting in over one million deaths annually, placing malaria among the most serious infectious diseases. Genomic and proteomic research of the clades of parasites containing Pf is progressing slowly and the functions of most of the ∼5300 genes are still unknown. We applied a 'bottom-up' comparative proteomic atomics analysis across the phylogenetic tree to visualize a protein molecule on its actual basis - i. e., its atomic level. We identified a protruding Pf3D7-specific U5MTase, determined its 3D protein structure, and identified potential inhibitory drug molecules through in silico drug screening that might serve as possible remedies for the treatment of malaria. Besides, this atomic-based proteome map provides a unique approach for the identification of parasite-specific proteins that could be considered as novel therapeutic targets.read more
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Phytochemical Profiling in Conjunction with In Vitro and In Silico Studies to Identify Human α-Amylase Inhibitors in Leucaena leucocephala (Lam.) De Wit for the Treatment of Diabetes Mellitus.
Senthil Renganathan,Sakthivel Manokaran,Preethi Vasanthakumar,Usha Singaravelu,Pok-Son Kim,Arne Kutzner,Klaus Heese +6 more
TL;DR: In this article, phytochemicals present in Leucaena leucocephala (Lam.) De Wit leaves were identified by gas chromatography-mass spectrometry and further examined by qualitative and quantitative methods.
Journal ArticleDOI
Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing.
Senthil Renganathan,Subrata Pramanik,Rajasekaran Ekambaram,Arne Kutzner,Pok-Son Kim,Klaus Heese +5 more
TL;DR: In this article, the authors determined a specific FAM72A-UNG2 heterodimer protein interaction using molecular docking and dynamics, and identified withaferin B as a molecule that can specifically prevent the FAM72a-unG2 interaction by blocking its cell signaling pathways.
References
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Journal ArticleDOI
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Garrett M. Morris,Ruth Huey,William Lindstrom,Michel F. Sanner,Richard K. Belew,David S. Goodsell,Arthur J. Olson +6 more
TL;DR: AutoDock4 incorporates limited flexibility in the receptor and its utility in analysis of covalently bound ligands is reported, using both a grid‐based docking method and a modification of the flexible sidechain technique.
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Journal ArticleDOI
Genome sequence of the human malaria parasite Plasmodium falciparum
Malcolm J. Gardner,Neil Hall,Eula Fung,Owen White,Matthew Berriman,Richard W. Hyman,Jane M. Carlton,Arnab Pain,Karen E. Nelson,Sharen Bowman,Ian T. Paulsen,Keith D. James,Jonathan A. Eisen,Kim Rutherford,Steven L. Salzberg,Alister Craig,Sue Kyes,Man Suen Chan,Vishvanath Nene,Shamira J. Shallom,Bernard B. Suh,Jeremy Peterson,Samuel V. Angiuoli,Mihaela Pertea,Jonathan E. Allen,Jeremy D. Selengut,Daniel H. Haft,Michael W. Mather,Akhil B. Vaidya,David M. A. Martin,Alan H. Fairlamb,Martin Fraunholz,David S. Roos,Stuart A. Ralph,Geoffrey I. McFadden,Leda M. Cummings,G. Mani Subramanian,Christopher J. Mungall,J. Craig Venter,Daniel J. Carucci,Stephen L. Hoffman,Chris I. Newbold,Ronald W. Davis,Claire M. Fraser,Bart Barrell +44 more
TL;DR: The genome sequence of P. falciparum clone 3D7 is reported, which is the most (A + T)-rich genome sequenced to date and is being exploited in the search for new drugs and vaccines to fight malaria.
Journal ArticleDOI
A semiempirical free energy force field with charge-based desolvation.
TL;DR: The authors describe the development and testing of a semiempirical free energy force field for use in AutoDock4 and similar grid‐based docking methods based on a comprehensive thermodynamic model that allows incorporation of intramolecular energies into the predicted free energy of binding.
Software News and Update A Semiempirical Free Energy Force Field with Charge-Based Desolvation
TL;DR: In this article, a semi-empirical free energy force field for use in AutoDock4 and similar grid-based docking methods is presented, based on a comprehensive thermodynamic model that allows incorporation of intramolecular energies into the predicted free energy of binding.
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