PDBsum entry: 1iir

Transferase

PDB id: 1iir

Contents

Protein chain

382 a.a. *

Ligands

SO4

Metals

_MG ×2

Waters ×293

* Residue conservation analysis

PDB id:

1iir

Name:

Transferase

Title:

Crystal structure of udp-glucosyltransferase gtfb

Structure:

Glycosyltransferase gtfb. Chain: a. Synonym: udp-glycosyltransferase gtfb. Engineered: yes

Source:

Amycolatopsis orientalis. Organism_taxid: 31958. Strain: a82846. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.80Å R-factor: 0.211 R-free: 0.231

Authors:

A.M.Mulichak,H.C.Losey,C.T.Walsh,R.M.Garavito

Key ref:

A.M.Mulichak et al. (2001). Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics. Structure, 9, 547-557. PubMed id: 11470430 DOI: 10.1016/S0969-2126(01)00616-5

Date:

24-Apr-01 Release date: 18-Jul-01

Protein chain

P96559  (P96559_AMYOR) -  Glycosyltransferase GtfB

Seq: 407 a.a.

Struc: 382 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: metabolic process (3 terms)
• Biochemical function: transferase activity (2 terms)

DOI no: 10.1016/S0969-2126(01)00616-5

Structure 9:547-557 (2001)

PubMed id: 11470430

Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics.

A.M.Mulichak, H.C.Losey, C.T.Walsh, R.M.Garavito.

ABSTRACT

BACKGROUND: Members of the vancomycin group of glycopeptide antibiotics have an oxidatively crosslinked heptapeptide scaffold decorated at the hydroxyl groups of 4-OH-Phegly4 or beta-OH-Tyr6 with mono- (residue 6) or disaccharides (residue 4). The disaccharide in vancomycin itself is L-vancosamine-1,2-glucose, and in chloroeremomycin it is L-4-epi-vancosamine-1,2-glucose. The sugars and their substituents play an important role in efficacy, particularly against vancomycin-resistant pathogenic enterococci. RESULTS: The glucosyltransferase, GtfB, that transfers the glucose residue from UDP-glucose to the 4-OH-Phegly4 residue of the vancomycin aglycone, initiating the glycosylation pathway in chloroeremomycin maturation, has been crystallized, and its structure has been determined by X-ray analysis at 1.8 A resolution. The enzyme has a two-domain structure, with a deep interdomain cleft identified as the likely site of UDP-glucose binding. A hydrophobic patch on the surface of the N-terminal domain is proposed to be the binding site of the aglycone substrate. Mutagenesis has revealed Asp332 as the best candidate for the general base in the glucosyltransfer reaction. CONCLUSIONS: The structure of GtfB places it in a growing group of glycosyltransferases, including Escherichia coli MurG and a beta-glucosyltransferase from T4 phage, which together form a subclass of the glycosyltransferase superfamily and give insights into the recognition of the NDP-sugar and aglycone cosubstrates. A single major interdomain linker between the N- and C- terminal domains suggests that reprogramming of sugar transfer or aglycone recognition in the antibiotic glycosyltransferases, including the glycopeptide and also the macrolide antibiotics, will be facilitated by this structural information.

Selected figure(s)

Figure 4.
Figure 4. Stereo View Showing Ribbon Diagrams of Homologous GtfB, MurG, and T4 b-GT StructuresA high degree of conservation of the b sheets (highlighted in blue) is clearly visible. In the T4 b-GT structure, the bound UDP is shown in red

The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 547-557) copyright 2001.

Figure was selected by the author.