PDBsum entry 3vms

Transferase

PDB id: 3vms

Contents

Protein chains

220 a.a.

PDB id:

3vms

Name:

Transferase

Title:

Crystal structure of staphylococcus aureus membrane-bound transglycosylase in complex with nbd-lipid ii

Structure:

Monofunctional glycosyltransferase. Chain: a, b. Fragment: residues 28-269. Synonym: mgt, peptidoglycan tgase. Engineered: yes

Source:

Staphylococcus aureus. Organism_taxid: 158878. Strain: mu50. Gene: mgt. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.20Å R-factor: 0.265 R-free: 0.330

Authors:

C.Y.Huang,H.W.Shih,L.Y.Lin,Y.W.Tien,T.J.R.Cheng,W.C.Cheng,C.H.Wong, C.Ma

Key ref:

C.Y.Huang et al. (2012). Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism. Proc Natl Acad Sci U S A, 109, 6496-6501. PubMed id: 22493270

Date:

15-Dec-11 Release date: 18-Apr-12

Protein chains

Q99T05  (MGT_STAAM) -  Monofunctional glycosyltransferase from Staphylococcus aureus (strain Mu50 / ATCC 700699)

Seq: 269 a.a.

Struc: 220 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.1.129 - Transferred entry: 2.4.99.28.
• Pathway: Peptidoglycan Biosynthesis (Part 3)
• Reaction: [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)](n)- di-trans,octa-cis-undecaprenyl diphosphate + beta-D-GlcNAc-(1->4)- Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa- cis-undecaprenyl diphosphate = [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D- Glu-L-Lys-D-Ala-D-Ala)](n+1)-di-trans-octa-cis-undecaprenyl diphosphate + di-trans,octa-cis-undecaprenyl diphosphate + H⁺

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

Key reference

Proc Natl Acad Sci U S A 109:6496-6501 (2012)

PubMed id: 22493270

Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism.

C.Y.Huang, H.W.Shih, L.Y.Lin, Y.W.Tien, T.J.Cheng, W.C.Cheng, C.H.Wong, C.Ma.

ABSTRACT

Bacterial transpeptidase and transglycosylase on the surface are essential for cell wall synthesis, and many antibiotics have been developed to target the transpeptidase; however, the problem of antibiotic resistance has arisen and caused a major threat in bacterial infection. The transglycosylase has been considered to be another excellent target, but no antibiotics have been developed to target this enzyme. Here, we determined the crystal structure of the Staphylococcus aureus membrane-bound transglycosylase, monofunctional glycosyltransferase, in complex with a lipid II analog to 2.3 Å resolution. Our results showed that the lipid II-contacting residues are not only conserved in WT and drug-resistant bacteria but also significant in enzymatic activity. Mechanistically, we proposed that K140 and R148 in the donor site, instead of the previously proposed E156, are used to stabilize the pyrophosphate-leaving group of lipid II, and E100 in the acceptor site acts as general base for the 4-OH of GlcNAc to facilitate the transglycosylation reaction. This mechanism, further supported by mutagenesis study and the structure of monofunctional glycosyltransferase in complex with moenomycin in the donor site, provides a direction for antibacterial drugs design.