PDBsum entry 3vfk

Sugar binding protein/antibiotic

PDB id: 3vfk

Contents

Protein chain

79 a.a.

Ligands

GHP-3MY-3FG-GHP-GHP-OMX-3FG

GCS-T55

NAG

MAN

Waters ×10

PDB id:

3vfk

Name:

Sugar binding protein/antibiotic

Title:

The structure of monodechloro-teicoplanin in complex with its ligand, using ubiquitin as a ligand carrier

Structure:

Ubiquitin, c-terminal fused by cys-lys-d-ala-d-ala. Chain: a. Synonym: ubiquitin. Engineered: yes. Monodechloro- teicoplanin a2-2. Chain: g

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ubc. Expressed in: escherichia coli. Expression_system_taxid: 562. Actinoplanes teichomyceticus. Organism_taxid: 1867

Resolution:

2.80Å R-factor: 0.279 R-free: 0.306

Authors:

N.J.Economou,S.D.Weeks,K.C.Grasty,P.J.Loll

Key ref:

N.J.Economou et al. (2013). Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach. Acta Crystallogr D Biol Crystallogr, 69, 520-533. PubMed id: 23519660 DOI: 10.1107/S0907444912050469

Date:

09-Jan-12 Release date: 09-Jan-13

Protein chain

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 79 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1107/S0907444912050469

Acta Crystallogr D Biol Crystallogr 69:520-533 (2013)

PubMed id: 23519660

Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach.

N.J.Economou, I.J.Zentner, E.Lazo, J.Jakoncic, V.Stojanoff, S.D.Weeks, K.C.Grasty, S.Cocklin, P.J.Loll.

ABSTRACT

Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a D-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein-peptide-antibiotic complex. The 2.05 Å resolution MBP-peptide-teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance.