3 research outputs found
Structural–Functional Studies of <i>Burkholderia cenocepacia</i> d‑Glycero-β‑d‑manno-heptose 7‑Phosphate Kinase (HldA) and Characterization of Inhibitors with Antibiotic Adjuvant and Antivirulence Properties
As an essential constituent of the outer membrane of
Gram-negative bacteria, lipopolysaccharide contributes significantly
to virulence and antibiotic resistance. The lipopolysaccharide biosynthetic
pathway therefore serves as a promising therapeutic target for antivirulence
drugs and antibiotic adjuvants. Here we report the structural–functional
studies of d-glycero-β-d-manno-heptose 7-phosphate
kinase (HldA), an absolutely conserved enzyme in this pathway, from <i>Burkholderia cenocepacia</i>. HldA is structurally similar to
members of the PfkB carbohydrate kinase family and appears to catalyze
heptose phosphorylation via an in-line mechanism mediated mainly by
a conserved aspartate, Asp270. Moreover, we report the structures
of HldA in complex with two potent inhibitors in which both inhibitors
adopt a folded conformation and occupy the nucleotide-binding sites.
Together, these results provide important insight into the mechanism
of HldA-catalyzed heptose phosphorylation and necessary information
for further development of HldA inhibitors
sj-pdf-1-wso-10.1177_17474930231205208 – Supplemental material for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial
Supplemental material, sj-pdf-1-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke</p
sj-pdf-2-wso-10.1177_17474930231205208 – Supplemental material for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial
Supplemental material, sj-pdf-2-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke</p