4U94

Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway

Summary for 4U94

• Entry DOI: 10.2210/pdb4u94/pdb
• Descriptor: Maltokinase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: mycobacterium vanbalenii, maltokinase, maltose, glycogen, appcp, transferase
• Biological source: Mycobacterium vanbaalenii
• Total number of polymer chains: 1
• Total formula weight: 49770.97

Authors

Fraga, J.,Empadinhas, N.,Pereira, P.J.B.,Macedo-Ribeiro, S. (deposition date: 2014-08-05, release date: 2015-02-11, Last modification date: 2024-05-08)

Primary citation

Fraga, J.,Maranha, A.,Mendes, V.,Pereira, P.J.,Empadinhas, N.,Macedo-Ribeiro, S.
Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway.
Sci Rep, 5:8026-8026, 2015

PubMed Abstract: A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 Å structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds.

PubMed: 25619172
DOI: 10.1038/srep08026

Experimental method

X-RAY DIFFRACTION (1.473 Å)