Structural highlights
Function
[BLE_STRHI] Binding protein with a strong affinity to the bleomycin family of antibiotics.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure and site-directed mutagenesis of a bleomycin resistance protein and their significance for drug sequestering.,Dumas P, Bergdoll M, Cagnon C, Masson JM EMBO J. 1994 Jun 1;13(11):2483-92. PMID:7516875[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dumas P, Bergdoll M, Cagnon C, Masson JM. Crystal structure and site-directed mutagenesis of a bleomycin resistance protein and their significance for drug sequestering. EMBO J. 1994 Jun 1;13(11):2483-92. PMID:7516875
