1KLL

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

1KLL の概要

• エントリーDOI: 10.2210/pdb1kll/pdb
• 関連するPDBエントリー: 1KMZ
• 分子名称: mitomycin-binding protein, 1,2-CIS-1-HYDROXY-2,7-DIAMINO-MITOSENE (3 entities in total)
• 機能のキーワード: mitomycin c, antibiotic resistance, sad, anomalous diffraction, domain swapping, p-staking, antimicrobial protein
• 由来する生物種: Streptomyces lavendulae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14892.19

構造登録者

Martin, T.W.,Dauter, Z.,Devedjiev, Y.,Sheffield, P.,Jelen, F.,He, M.,Sherman, D.,Otlewski, J.,Derewenda, Z.S.,Derewenda, U. (登録日: 2001-12-12, 公開日: 2002-07-19, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.5 Å)