1kmz

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Image:1kmz.gif


PDB ID 1kmz

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, resolution 1.50Å
Related: 1KLL


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



MOLECULAR BASIS OF MITOMYCIN C RESICTANCE IN STREPTOMYCES: CRYSTAL STRUCTURES OF THE MRD PROTEIN WITH AND WITHOUT A DRUG DERIVATIVE


Overview

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.

About this Structure

1KMZ is a Single protein structure of sequence from Streptomyces lavendulae. Full crystallographic information is available from OCA.

Reference

Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein., Martin TW, Dauter Z, Devedjiev Y, Sheffield P, Jelen F, He M, Sherman DH, Otlewski J, Derewenda ZS, Derewenda U, Structure. 2002 Jul;10(7):933-42. PMID:12121648

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