title: Homotypic dimerization of a maltose kinase for molecular scaffolding.
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.
authors.affiliation: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China [2].
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China [2].
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Guan
authors.affiliation: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China [2] Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin. 300071, China.
authors.forename: Neil
authors.initials: N
authors.lastname: Shaw
authors.affiliation: Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin. 300071, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University. 310036, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing. 100101, China [2] Structure Biology Laboratory, Tsinghua University, Beijing. 100084, China [3] Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin. 300071, China.
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D008320:Maltose / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010766:Phosphorylation; D011487:Protein Conformation; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D009004:Monosaccharide Transport Proteins; D011994:Recombinant Proteins; D008320:Maltose