Database accession: MF7000844
Name: Bleomycin-binding protein (Streptoalloteichus hindustanus)
PDB ID: 1byl
Experimental method: X-ray (2.30 Å)
Assembly: Homodimer
Source organism: Streptoalloteichus hindustanus
Primary publication of the structure:
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.
(1994) EMBO J. 13: 2483-92
PMID: 7516875
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
Biological process:
response to antibiotic response to antibiotic
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Bleomycin resistance protein
Source organism: Streptoalloteichus hindustanus
Length: 124 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAKLTSAVPVLTARDVAGAVEFWTDRLGFSRDFVEDDFAGVVRDDVTLFISAVQDQVVPDNTLAWVWVRGLDELYAEWSEVVSTNFRDASGPAMTEIGEQPWGREFALRDPAGNCVHFVAEEQD
UniProtKB AC: P17493 (positions: 1-121)
Coverage: 97%
Name: Bleomycin resistance protein
Source organism: Streptoalloteichus hindustanus
Length: 124 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAKLTSAVPVLTARDVAGAVEFWTDRLGFSRDFVEDDFAGVVRDDVTLFISAVQDQVVPDNTLAWVWVRGLDELYAEWSEVVSTNFRDASGPAMTEIGEQPWGREFALRDPAGNCVHFVAEEQD
UniProtKB AC: P17493 (positions: 1-121)
Coverage: 97%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Glyoxalase superfamily
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The bleomycin resistance protein forms a tight dimer with a large hydrophobic interface and domain-swapping involving the N-terminal end of both monomers. Only dimeric form could be detected in solution by several dedicated methods. The antibiotic binds to he dimer interface contacting both monomers (PMID:7516875). Temperature-induced equilibrium unfolding experiments on the Shble protein and its engineered variants suggested a two-state model of unfolding (although unfolding was largely irreversible with only 40% of the native folded signal regained during the refolding phase) and the strong stabilizing effect of bleomycin on the dimer based on largely increased thermostability of the protein in the presence of the antibiotic (PMID:15640151).
Chain A:
N/A
Chain A-2:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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