1BYL

BLEOMYCIN RESISTANCE PROTEIN FROM STREPTOALLOTEICHUS HINDUSTANUS

Summary for 1BYL

• Entry DOI: 10.2210/pdb1byl/pdb
• Descriptor: PROTEIN (BLEOMYCIN RESISTANCE PROTEIN) (2 entities in total)
• Functional Keywords: antibiotic resistance, bleomycin, drug sequestering, chain swapping, antibiotic
• Biological source: Streptoalloteichus hindustanus
• Total number of polymer chains: 1
• Total formula weight: 13953.39

Authors

Dumas, P.,Bergdoll, M.,Cagnon, C.,Masson, J.M. (deposition date: 1998-10-17, release date: 1999-10-21, Last modification date: 2024-02-07)

Primary citation

Dumas, P.,Bergdoll, M.,Cagnon, C.,Masson, J.M.
Crystal structure and site-directed mutagenesis of a bleomycin resistance protein and their significance for drug sequestering.
EMBO J., 13:2483-2492, 1994

PubMed Abstract: The antibiotic bleomycin, a strong DNA cutting agent, is naturally produced by actinomycetes which have developed a resistance mechanism against such a lethal compound. The crystal structure, at 2.3 A resolution, of a bleomycin resistance protein of 14 kDa reveals a structure in two halves with the same alpha/beta fold despite no sequence similarity. The crystal packing shows compact dimers with a hydrophobic interface and involved in mutual chain exchange. Two independent solution studies (analytical centrifugation and light scattering) showed that this dimeric form is not a packing artefact but is indeed the functional one. Furthermore, light scattering also showed that one dimer binds two antibiotic molecules as expected. A crevice located at the dimer interface, as well as the results of a site-directed mutagenesis study, led to a model wherein two bleomycin molecules are completely sequestered by one dimer. This provides a novel insight into antibiotic resistance due to drug sequestering, and probably also into drug transport and excretion.

PubMed: 7516875

Experimental method

X-RAY DIFFRACTION (2.3 Å)