3ZT6: Glge Isoform 1 From Streptomyces Coelicolor With Alpha- Cyclodextrin And Maltose Bound

GlgE is a recently identified (1-->4)-alpha-d-glucan:phosphate alpha-d-maltosyltransferase involved in alpha-glucan biosynthesis in bacteria and is a genetically validated anti-tuberculosis drug target. It is a member of the GH13_3 CAZy subfamily for which no structures were previously known. We have solved the structure of GlgE isoform I from Streptomyces coelicolor and shown that this enzyme has the same catalytic and very similar kinetic properties to GlgE from Mycobacterium tuberculosis. The S. coelicolor enzyme forms a homodimer with each subunit comprising five domains, including a core catalytic alpha-amylase-type domain A with a (beta/alpha)(8) fold. This domain is elaborated with domain B and two inserts that are specifically configured to define a well conserved donor pocket capable of binding maltose. Domain A, together with domain N from the neighboring subunit, forms a hydrophobic patch that is close to the maltose-binding site and capable of binding cyclodextrins. Cyclodextrins competitively inhibit the binding of maltooligosaccharides to the S. coelicolor enzyme, showing that the hydrophobic patch overlaps with the acceptor binding site. This patch is incompletely conserved in the M. tuberculosis enzyme such that cyclodextrins do not inhibit this enzyme, despite acceptor length specificity being conserved. The crystal structure reveals two further domains, C and S, the latter being a helix bundle not previously reported in GH13 members. The structure provides a framework for understanding how GlgE functions and will help guide the development of inhibitors with therapeutic potential.
PDB ID: 3ZT6Download
MMDB ID: 93615
PDB Deposition Date: 2011/7/1
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 2.19  Å
Source Organism:
Similar Structures:
Biological Unit for 3ZT6: dimeric; determined by author and by software (PISA)
Molecular Components in 3ZT6
Label Count Molecule
Proteins (2 molecules)
Putative Glucanohydrolase Pep1a(Gene symbol: SCO5443)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB