PDBsum entry 4u3c

Transferase

PDB id: 4u3c

Contents

Protein chains

(+ 0 more) 660 a.a.

Ligands

GLC-GLC ×6

GLC-GLC-GLC-GLC-GLC-GLC ×6

PDB id:

4u3c

Name:

Transferase

Title:

Docking site of maltohexaose in the mtb glge

Structure:

Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase. Chain: a, b, c, d, e, f. Synonym: gmpmt,(1->4)-alpha-d-glucan:maltose-1-phosphate alpha-d- maltosyltransferase,(1->4)-alpha-d-glucan:phosphate alpha-d- maltosyltransferase. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 83331. Strain: cdc 1551 / oshkosh. Gene: glge, mt1369. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

3.98Å R-factor: 0.225 R-free: 0.256

Authors:

D.R.Ronning,J.J.Lindenberger

Key ref:

J.J.Lindenberger et al. (2015). Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors. Sci Rep, 5, 12830. PubMed id: 26245983 DOI: 10.1038/srep12830

Date:

19-Jul-14 Release date: 22-Jul-15

Protein chains

P9WQ16  (GLGE_MYCTO) -  Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase from Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)

Seq: 701 a.a.

Struc: 660 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.99.16 - starch synthase (maltosyl-transferring).
• Reaction: alpha-maltose 1-phosphate + [(1->4)-alpha-D-glucosyl](n) = [(1->4)-alpha- D-glucosyl](n+2) + phosphate

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

Key reference

DOI no: 10.1038/srep12830

Sci Rep 5:12830 (2015)

PubMed id: 26245983

Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors.

J.J.Lindenberger, S.K.Veleti, B.N.Wilson, S.J.Sucheck, D.R.Ronning.

ABSTRACT

GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution, and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds, and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors.