1KLL

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

Summary for 1KLL

• Entry DOI: 10.2210/pdb1kll/pdb
• Related: 1KMZ
• Descriptor: mitomycin-binding protein, 1,2-CIS-1-HYDROXY-2,7-DIAMINO-MITOSENE (3 entities in total)
• Functional Keywords: mitomycin c, antibiotic resistance, sad, anomalous diffraction, domain swapping, p-staking, antimicrobial protein
• Biological source: Streptomyces lavendulae
• Total number of polymer chains: 1
• Total formula weight: 14892.19

Authors

Martin, T.W.,Dauter, Z.,Devedjiev, Y.,Sheffield, P.,Jelen, F.,He, M.,Sherman, D.,Otlewski, J.,Derewenda, Z.S.,Derewenda, U. (deposition date: 2001-12-12, release date: 2002-07-19, Last modification date: 2024-11-20)

Primary citation

Martin, T.W.,Dauter, Z.,Devedjiev, Y.,Sheffield, P.,Jelen, F.,He, M.,Sherman, D.H.,Otlewski, J.,Derewenda, Z.S.,Derewenda, U.
Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein.
Structure, 10:933-942, 2002

PubMed Abstract: 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.

PubMed: 12121648
DOI: 10.1016/S0969-2126(02)00778-5

Experimental method

X-RAY DIFFRACTION (1.5 Å)