Structure of ristocetin A in complex with a bacterial cell-wall mimetic.
Antimicrobial drug resistance is a serious public health problem and the development of new antibiotics has become an important priority. Ristocetin A is a class III glycopeptide antibiotic that is used in the diagnosis of von Willebrand disease and which has served as a lead compound for the development of new antimicrobial therapeutics. The 1.0 A resolution crystal structure of the complex between ristocetin A and a bacterial cell-wall peptide has been determined. As is observed for most other glycopeptide antibiotics, it is shown that ristocetin A forms a back-to-back dimer containing concave binding pockets that recognize the cell-wall peptide. A comparison of the structure of ristocetin A with those of class I glycopeptide antibiotics such as vancomycin and balhimycin identifies differences in the details of dimerization and ligand binding. The structure of the ligand-binding site reveals a likely explanation for ristocetin A's unique anticooperativity between dimerization and ligand binding.
Nahoum
Virginie
V
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Spector
Sherri
S
Loll
Patrick J
PJ
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D032701:Biomimetics / Q000639:trends; D002473:Cell Wall / Q000737:chemistry; D003460:Crystallization; D019281:Dimerization; D015195:Drug Design; D006801:Humans; D008024:Ligands; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus; D011485:Protein Binding; D011487:Protein Conformation; D012310:Ristocetin / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy; D014640:Vancomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D014965:X-Rays
D000900:Anti-Bacterial Agents; D008024:Ligands; D012310:Ristocetin; C087127:balhimycin; C016719:ristocetin A; D014640:Vancomycin