Homotypic dimerization of a maltose kinase for molecular scaffolding

Sci Rep. 2014 Sep 23:4:6418. doi: 10.1038/srep06418.

Abstract

Mycobacterium tuberculosis (Mtb) uses maltose-1-phosphate to synthesize α-glucans that make up the major component of its outer capsular layer. Maltose kinase (MaK) catalyzes phosphorylation of maltose. The molecular basis for this phosphorylation is currently not understood. Here, we describe the first crystal structure of MtbMaK refined to 2.4 Å resolution. The bi-modular architecture of MtbMaK reveals a remarkably unique N-lobe. An extended sheet protrudes into ligand binding pocket of an adjacent monomer and contributes residues critical for kinase activity. Structure of the complex of MtbMaK bound with maltose reveals that maltose binds in a shallow cavity of the C-lobe. Structural constraints permit phosphorylation of α-maltose only. Surprisingly, instead of a Gly-rich loop, MtbMaK employs 'EQS' loop to tether ATP. Notably, this loop is conserved across all MaK homologues. Structures of MtbMaK presented here unveil features that are markedly different from other kinases and support the scaffolding role proposed for this kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Crystallization
  • Crystallography, X-Ray
  • Maltose / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Monosaccharide Transport Proteins / chemistry*
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Mycobacterium tuberculosis / enzymology*
  • Phosphorylation
  • Protein Conformation
  • Protein Multimerization
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Monosaccharide Transport Proteins
  • Recombinant Proteins
  • Maltose

Associated data

  • PDB/4O7O
  • PDB/4O7P