PDBsum entry 4wzy

Transferase

PDB id: 4wzy

Contents

Protein chain

451 a.a.

Ligands

ATP

Metals

_MG

Waters ×499

References listed in PDB file

Key reference

• Title: Structure of mycobacterial maltokinase, The missing link in the essential glge-Pathway.
• Authors: J.Fraga, A.Maranha, V.Mendes, P.J.Pereira, N.Empadinhas, S.Macedo-Ribeiro.
• Ref.: Sci Rep, 2015, 5, 8026.
• PubMed id: 25619172

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.