Ashraf B Abdel-Naim, Pawan Kumar, Mohammed A Bazuhair, Waleed Y Rizg, Hatoon A Niyazi, Khalil Alkuwaity, Hanouf A Niyazi, Saif A Alharthy, Steve Harakeh, Shafiul Haque, Amresh Prakash, Vijay Kumar
The activity of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) is essential for the biosynthesis of sialic acid, which is involved in cellular processes in health and diseases. GNE contains an N-terminal epimerase domain and a C-terminal kinase domain (N-acetylmannosamine kinase, MNK). Mutations of the GNE protein led to hypoactivity of the enzyme and cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. Here, we used all-atom molecular dynamics (MD) simulations to comprehend the folding, dynamics and conformational stability of MNK variants, including the wild type (WT) and three mutants (H677R, V696M and H677R/V696M)...
March 19, 2024: Journal of Biomolecular Structure & Dynamics