Evidence map›Paper›PMID 26592566›Full record

ArticleNature communications2015

Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation.

Lionel Ballut, Sébastien Violot, Santosh Shivakumaraswamy, Lakshmi Prasoona Thota, Manu Sathya, Jyothirmai Kunala, Bauke W Dijkstra, Raphaël Terreux, Richard Haser, Hemalatha Balaram and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
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  7. Article
  8. Mapping of CaPP2C35 involved in the formation of light-green immature pepper (Capsicum annuum L.) fruits via GWAS and BSA.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2022
    Article
  9. Review
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  14. Inverse docking based screening and identification of protein targets for Cassiarin alkaloids againstSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2018
    Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Lionel BallutBioCrystallography and Structural Biology of Therapeutic Targets Group, Molecular and Structural Bases of Infectious Systems, UMR5086 CNRS-University of Lyon 1, 7 passage du Vercors, 69367 Lyon Cedex 07, France.
Sébastien ViolotBioCrystallography and Structural Biology of Therapeutic Targets Group, Molecular and Structural Bases of Infectious Systems, UMR5086 CNRS-University of Lyon 1, 7 passage du Vercors, 69367 Lyon Cedex 07, France.
Santosh ShivakumaraswamyMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Lakshmi Prasoona ThotaMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Manu SathyaMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Jyothirmai KunalaMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Bauke W DijkstraLaboratory of Biophysical Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.ORCID http://orcid.org/0000-0001-9731-6586
Raphaël TerreuxBioinformatics: Structures and Interactions Group, Molecular and Structural Bases of Infectious Systems, UMR5086 CNRS-University of Lyon 1, 7 passage du Vercors, 69367 Lyon Cedex 07, France.
Richard HaserBioCrystallography and Structural Biology of Therapeutic Targets Group, Molecular and Structural Bases of Infectious Systems, UMR5086 CNRS-University of Lyon 1, 7 passage du Vercors, 69367 Lyon Cedex 07, France.
Hemalatha BalaramMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Nushin AghajariBioCrystallography and Structural Biology of Therapeutic Targets Group, Molecular and Structural Bases of Infectious Systems, UMR5086 CNRS-University of Lyon 1, 7 passage du Vercors, 69367 Lyon Cedex 07, France.ORCID http://orcid.org/0000-0002-2245-2679

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85° rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371-375 holding catalytic residues and in loop 376-401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.

Indexed as

Carbon-Nitrogen LigasesCatalytic DomainEnzymesGlutamineKineticsModels, MolecularPlasmodium falciparumProtein ConformationProtein Structure, TertiaryProtozoan ProteinsCarbon-Nitrogen LigasesEnzymesGlutamineGMP synthase (glutamine-hydrolyzing)Protozoan Proteins

Identifiers

PMID26592566
PMCPMC4673825

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.