3HZS

S. aureus monofunctional glycosyltransferase (MtgA)in complex with moenomycin

Summary for 3HZS

• Entry DOI: 10.2210/pdb3hzs/pdb
• Related: 2C6W 2OLU 2OLV 2ZC5 3DWK
• Descriptor: Monofunctional glycosyltransferase, MOENOMYCIN, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: transglycosylase, peptidoglycan, monofunctional, moenomycin, cell membrane, cell shape, cell wall biogenesis/degradation, glycosyltransferase, membrane, peptidoglycan synthesis, transferase, transmembrane
• Biological source: Staphylococcus aureus subsp. aureus
• Cellular location: Cell membrane; Single-pass membrane protein (By similarity): Q7A0I6
• Total number of polymer chains: 1
• Total formula weight: 25936.42

Authors

Heaslet, H.,Miller, A.A.,Shaw, B.,Mistry, A. (deposition date: 2009-06-24, release date: 2009-07-07, Last modification date: 2024-04-03)

Primary citation

Heaslet, H.,Shaw, B.,Mistry, A.,Miller, A.A.
Characterization of the active site of S. aureus monofunctional glycosyltransferase (Mtg) by site-directed mutation and structural analysis of the protein complexed with moenomycin
J.Struct.Biol., 167:129-135, 2009

PubMed Abstract: Bacterial cell wall transglycosylases (TGs) and transpeptidases (TPs) are ideal drug targets due to their essentiality, accessibility and lack of mammalian homologs. Although antibacterial therapy using the beta-lactam family of TP inhibitors has been successful for decades, potent TG inhibitors which are suitable for development into antibiotics for human use have yet to be identified. We sought to further understand the molecular interactions required to inhibit bacterial transglycosylation by characterizing the active site of Staphylococcus aureus (Sa) monofunctional transglycosylase (Mtg). Ten mutants were tested for their ability to polymerize Lipid II and to crystallize in the presence of moenomycin. Five of six putative active site mutants (E100Q, D101N, Q136E, E156T, and Y176F) were found to be catalytically inactive whereas a F104Y mutation did not affect activity. Four mutants generated to enhance crystal formation (F143T, V154T, L157T, and F158T) also retained activity. Here we also report the crystal structure of Sa Mtg E100Q mutant in complex with the inhibitor moenomycin to 2.1A resolution. The co-crystal structure revealed detailed interactions between the protein and inhibitor including portions of the polycarbon tail of moenomycin. The structure also contained an ordered phosphate ion which helped to identify the Lipid II binding site.

PubMed: 19416756
DOI: 10.1016/j.jsb.2009.04.010

Experimental method

X-RAY DIFFRACTION (2.1 Å)