5VSJ

Sco GlgEI-V279S in complex with a pyrolidene-based ethyl-phosphonate compound

Summary for 5VSJ

• Entry DOI: 10.2210/pdb5vsj/pdb
• Related: 5VT4
• Descriptor: Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase 1, {2-[(2R,3R,4R,5R)-3-(alpha-D-glucopyranosyloxy)-4-hydroxy-2,5-bis(hydroxymethyl)pyrrolidin-1-yl]ethyl}phosphonic acid, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: streptomyces coelicolor, maltosyltransferase, transition state analogue, alpha-1, 4-glucan, transferase
• Biological source: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
• Total number of polymer chains: 2
• Total formula weight: 149347.10

Authors

Petit, C.,Ronning, D.R. (deposition date: 2017-05-11, release date: 2017-05-31, Last modification date: 2023-10-04)

Primary citation

Veleti, S.K.,Petit, C.,Ronning, D.R.,Sucheck, S.J.
Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S.
Org. Biomol. Chem., 15:3884-3891, 2017

PubMed Abstract: We synthesized and evaluated new zwitterionic inhibitors against glycoside hydrolase-like phosphorylase Streptomyces coelicolor (Sco) GlgEI-V279S which plays a role in α-glucan biosynthesis. Sco GlgEI-V279S serves as a model enzyme for validated anti-tuberculosis (TB) target Mycobacterium tuberculosis (Mtb) GlgE. Pyrrolidine inhibitors 5 and 6 were designed based on transition state considerations and incorporate a phosphonate on the pyrrolidine moiety to expand the interaction network between the inhibitor and the enzyme active site. Compounds 5 and 6 inhibited Sco GlgEI-V279S with K = 45 ± 4 μM and 95 ± 16 μM, respectively, and crystal structures of Sco GlgE-V279S-5 and Sco GlgE-V279S-6 were obtained at a 3.2 Å and 2.5 Å resolution, respectively.

PubMed: 28422240
DOI: 10.1039/c7ob00388a

Experimental method

X-RAY DIFFRACTION (2.456 Å)