1kmz
From Proteopedia
(New page: 200px<br /><applet load="1kmz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kmz, resolution 1.50Å" /> '''MOLECULAR BASIS OF M...) |
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| - | [[Image:1kmz.gif|left|200px]]<br /><applet load="1kmz" size=" | + | [[Image:1kmz.gif|left|200px]]<br /><applet load="1kmz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kmz, resolution 1.50Å" /> | caption="1kmz, resolution 1.50Å" /> | ||
'''MOLECULAR BASIS OF MITOMYCIN C RESICTANCE IN STREPTOMYCES: CRYSTAL STRUCTURES OF THE MRD PROTEIN WITH AND WITHOUT A DRUG DERIVATIVE'''<br /> | '''MOLECULAR BASIS OF MITOMYCIN C RESICTANCE IN STREPTOMYCES: CRYSTAL STRUCTURES OF THE MRD PROTEIN WITH AND WITHOUT A DRUG DERIVATIVE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mitomycin C (MC) is a potent anticancer agent. Streptomyces lavendulae, which produces MC, protects itself from the lethal effects of the drug by | + | 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== | ==About this Structure== | ||
| - | 1KMZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_lavendulae Streptomyces lavendulae]. Full crystallographic information is available from [http:// | + | 1KMZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_lavendulae Streptomyces lavendulae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Dauter, Z.]] | [[Category: Dauter, Z.]] | ||
[[Category: Derewenda, U.]] | [[Category: Derewenda, U.]] | ||
| - | [[Category: Derewenda, Z | + | [[Category: Derewenda, Z S.]] |
[[Category: Devedjiev, Y.]] | [[Category: Devedjiev, Y.]] | ||
[[Category: He, M.]] | [[Category: He, M.]] | ||
[[Category: Jelen, F.]] | [[Category: Jelen, F.]] | ||
| - | [[Category: Martin, T | + | [[Category: Martin, T W.]] |
[[Category: Otlewski, J.]] | [[Category: Otlewski, J.]] | ||
[[Category: Sheffield, P.]] | [[Category: Sheffield, P.]] | ||
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[[Category: sad]] | [[Category: sad]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:52 2008'' |
Revision as of 11:35, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 13:35:52 2008
Categories: Single protein | Streptomyces lavendulae | Dauter, Z. | Derewenda, U. | Derewenda, Z S. | Devedjiev, Y. | He, M. | Jelen, F. | Martin, T W. | Otlewski, J. | Sheffield, P. | Sherman, D. | Anomalous diffraction | Antibiotic resistance | Crystal structure | Domain swapping | Mitomycin c | P-staking | Sad
