1KLL: Molecular basis of mitomycin C resictance in streptomyces: Crystal structures of the MRD protein with and without a drug derivative

Mitomycin C (MC) is a potent anticancer agent. Streptomyces lavendulae, which produces MC, protects itself from the lethal effects of the drug by expressing several resistance proteins. One of them (MRD) binds MC and functions as a drug exporter. We report the crystal structure of MRD and its complex with an MC metabolite, 1,2-cis-1-hydroxy-2,7-diaminomitosene, at 1.5 A resolution. The drug is sandwiched by pi-stacking interactions of His-38 and Trp-108. MRD is a dimer. The betaalphabetabetabeta fold of the MRD molecule is reminiscent of methylmalonyl-CoA epimerase, bleomycin resistance proteins, glyoxalase I, and extradiol dioxygenases. The location of the binding site is identical to the ones in evolutionarily related enzymes, suggesting that the protein may have been recruited from a different metabolic pathway.
PDB ID: 1KLLDownload
MMDB ID: 71161
PDB Deposition Date: 2001/12/12
Updated in MMDB: 2018/06
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 1KLL: dimeric; determined by author and by software (PISA)
Molecular Components in 1KLL
Label Count Molecule
Proteins (2 molecules)
Mitomycin-binding Protein
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

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