PDBsum entry 4wzy

Transferase

PDB id: 4wzy

Contents

Protein chain

451 a.a.

Ligands

ATP

Metals

_MG

Waters ×499

PDB id:

4wzy

Name:

Transferase

Title:

Structure of mycobacterial maltokinase, the missing link in the essential glge-pathway (atp complex)

Structure:

Maltokinase. Chain: a. Synonym: mak,maltose-1-phosphate synthase. Engineered: yes

Source:

Mycobacterium vanbaalenii. Organism_taxid: 350058. Strain: dsm 7251 / pyr-1. Gene: mak, mvan_5735. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

1.71Å R-factor: 0.178 R-free: 0.205

Authors:

J.Fraga,N.Empadinhas,P.J.B.Pereira,S.Macedo-Ribeiro

Key ref:

J.Fraga et al. (2015). Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway. Sci Rep, 5, 8026. PubMed id: 25619172

Date:

20-Nov-14 Release date: 11-Feb-15

Protein chain

A1TH50  (MAK_MYCVP) -  Maltokinase from Mycolicibacterium vanbaalenii (strain DSM 7251 / JCM 13017 / BCRC 16820 / KCTC 9966 / NRRL B-24157 / PYR-1)

Seq: 441 a.a.

Struc: 451 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.175 - maltokinase.
• Reaction: D-maltose + ATP = alpha-maltose 1-phosphate + ADP + H⁺

D-maltose + ATP = alpha-maltose 1-phosphate (Bound ligand (Het Group name = ATP) matches with 85.19% similarity) + ADP + H(+)

• Cofactor: Mg(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Sci Rep 5:8026 (2015)

PubMed id: 25619172

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

J.Fraga, A.Maranha, V.Mendes, P.J.Pereira, N.Empadinhas, S.Macedo-Ribeiro.

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.