Metabolic insights into phosphofructokinase inhibition in bloodstream-form trypanosomes

Autor: Zandile Nare, Tessa Moses, Karl Burgess, Achim Schnaufer, Malcolm D. Walkinshaw, Paul A. M. Michels

Publikováno v: Frontiers in Cellular and Infection Microbiology, Vol 13 (2023)

Previously, we reported the development of novel small molecules that are potent inhibitors of the glycolytic enzyme phosphofructokinase (PFK) of Trypanosoma brucei and related protists responsible for serious diseases in humans and domestic animals.

Externí odkaz: https://doaj.org/article/e22a5f125b2a483da392dcbbf91fccdd

Allosteric pyruvate kinase-based 'logic gate' synergistically senses energy and sugar levels in Mycobacterium tuberculosis

Autor: Wenhe Zhong, Liang Cui, Boon Chong Goh, Qixu Cai, Peiying Ho, Yok Hian Chionh, Meng Yuan, Abbas El Sahili, Linda A. Fothergill-Gilmore, Malcolm D. Walkinshaw, Julien Lescar, Peter C. Dedon

Publikováno v: Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017)

Pyruvate kinase (PYK) controls glycolytic flux. Here, the authors combine biochemical, structural and computational modelling studies to characterize the allosteric mechanisms regulating Mycobacterium tuberculosis PYK activity and show that AMP and g

Externí odkaz: https://doaj.org/article/1ccbb8a01a5d4d8c9f866502136c19e3

Structures of pyruvate kinases display evolutionarily divergent allosteric strategies

Autor: Hugh P. Morgan, Wenhe Zhong, Iain W. McNae, Paul A. M. Michels, Linda A. Fothergill-Gilmore, Malcolm D. Walkinshaw

Publikováno v: Royal Society Open Science, Vol 1, Iss 1 (2014)

The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8° rigid body rocking motion of the A- and C-domain cores in each of the fo

Externí odkaz: https://doaj.org/article/b7411e07cd9e47569f4972c21c4a6542

Peripheral blood immune cell profiling of acute corneal transplant rejection

Autor: Jesper Hjortdal, Matthew D. Griffin, Marion Cadoux, W. John Armitage, Max Bylesjo, Peadar Mac Gabhann, Conor C. Murphy, Uwe Pleyer, Derek Tole, Bertrand Vabres, Malcolm D. Walkinshaw, Pierre-Antoine Gourraud, Matilde Karakachoff, Sophie Brouard, Nicolas Degauque

Publikováno v: Hjortdal, J, Griffin, M D, Cadoux, M, Armitage, W J, Bylesjo, M, Mac Gabhann, P, Murphy, C C, Pleyer, U, Tole, D, Vabres, B, Walkinshaw, M D, Gourraud, P-A, Karakachoff, M, Brouard, S & Degauque, N 2022, ' Peripheral blood immune cell profiling of acute corneal transplant rejection ', American Journal of Transplantation, vol. 22, no. 10, pp. 2337-2347 . https://doi.org/10.1111/ajt.17119
Hjortdal, J, Griffin, M D, Cadoux, M, Armitage, W J, Bylesjo, M, Gabhann, P M, Murphy, C C, Pleyer, U, Tole, D, Vabres, B, Walkinshaw, M D, Gourraud, PA, Karakachoff, M, Brouard, S & Degauque, N 2022, ' Peripheral blood immune cell profiling of acute corneal transplant rejection ', American Journal of Transplantation, vol. 22, no. 10, pp. 2337-2347 . https://doi.org/10.1111/ajt.17119

Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples w

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13a6ad3ef6c845b28fc6e71b4549af5d
https://pure.au.dk/portal/da/publications/peripheral-blood-immune-cell-profiling-of-acute-corneal-transplant-rejection(bf3eab5b-a0e6-4b9b-b230-13daa710c3bf).html

Kinetic and structural studies of Trypanosoma and Leishmania phosphofructokinases show evolutionary divergence and identify AMP as a switch regulating glycolysis versus gluconeogenesis

Autor: James Kinkead, Malcolm D. Walkinshaw, Martin A. Wear, Monserrat Vásquez-Valdivieso, Iain W. McNae, Peter M Fernandes, Paul A.M. Michels

Publikováno v: The Febs Journal
Fernandes, P, Kinkead, J, McNae, I, Vásquez-Valdivieso, M G, Wear, M, Michels, P & Walkinshaw, M 2019, ' Kinetic and structural studies of Trypanosoma and Leishmania phosphofructokinases show evolutionary divergence and identify AMP as a switch regulating glycolysis versus gluconeogenesis ', Febs Journal . https://doi.org/10.1111/febs.15177

Trypanosomatids possess glycosome organelles that contain much of the glycolytic machinery, including phosphofructokinase (PFK). We present kinetic and structural data for PFK from three human pathogenic trypanosomatids, illustrating intriguing diffe

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e0ea2f8a7ecd2ee01abc1225b75b567
http://europepmc.org/articles/PMC7383607