Probing the structural dynamics of the Plasmodium falciparum tunneling-fold enzyme 6-pyruvoyl tetrahydropterin synthase to reveal allosteric drug targeting sites:

Khairallah, Afrah; Ross, Caroline J; Tastan Bishop, Özlem

Title: Probing the structural dynamics of the Plasmodium falciparum tunneling-fold enzyme 6-pyruvoyl tetrahydropterin synthase to reveal allosteric drug targeting sites:
Creator: Khairallah, Afrah
Creator: Ross, Caroline J
Creator: Tastan Bishop, Özlem
Date Issued: 2020
Date: 2020
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/163057
Identifier: vital:41008
Identifier: https://doi.org/10.3389/fmolb.2020.575196
Description: The de novo folate synthesis pathway is a well-established drug target in the treatment of many infectious diseases. Antimalarial antifolate drugs have proven to be effective against malaria, however, rapid drug resistance has emerged on the two primary targeted enzymes: dihydrofolate reductase and dihydroptoreate synthase. The need to identify alternative antifolate drugs and novel metabolic targets is of imminent importance. The 6-pyruvol tetrahydropterin synthase (PTPS) enzyme belongs to the tunneling fold protein superfamily which is characterized by a distinct central tunnel/cavity. The enzyme catalyzes the second reaction step of the parasite’s de novo folate synthesis pathway and is responsible for the conversion of 7,8-dihydroneopterin to 6-pyruvoyl-tetrahydropterin. In this study, we examine the structural dynamics of Plasmodium falciparum PTPS using the anisotropic network model, to elucidate the collective motions that drive the function of the enzyme and identify potential sites for allosteric modulation of its binding properties.
Format: 18 pages
Format: pdf
Language: English
Relation: Frontiers in Molecular Biosciences
Relation: Khairallah, A., Ross, C.J. and Tastan Bishop, O., 2020. Probing the structural dynamics of the Plasmodium falciparum tunneling-fold enzyme 6-pyruvoyl tetrahydropterin synthase to reveal allosteric drug targeting sites. Frontiers in Molecular Biosciences, 7, p.246-263
Relation: Frontiers in Molecular Biosciences volume number 246 263 September 2020 2296-889X
Rights: Publisher
Rights: Use of this resource is governed by the terms and conditions of the Frontiers in Molecular Biosciences Terms and Conditions Statement (https://www.frontiersin.org/legal/terms-and-conditions)

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Tastan Bishop, Ozlem (Prof)

RU Research Unit in Bioinformatics (RUBi)

SDG 03. Good Health and Well-Being

RU Department of Biochemistry, Microbiology and Bioinformatics

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