1zxf
From Proteopedia
| Line 11: | Line 11: | ||
'''Solution structure of a self-sacrificing resistance protein, CalC from Micromonospora echinospora''' | '''Solution structure of a self-sacrificing resistance protein, CalC from Micromonospora echinospora''' | ||
| + | |||
| + | ==Overview== | ||
| + | The recent discovery of the first "self-sacrifice" mechanism for bacterial resistance to the enediyne antitumor antibiotics, where enediyne-induced proteolysis of the resistance protein CalC inactivates both the highly reactive metabolite and the resistance protein, revealed yet another ingenious bacterial mechanism for controlling reactive metabolites. As reported herein, the first 3D structures of CalC and CalC in complex with calicheamicin (CLM) divulge CalC to be a member of the steroidogenic acute regulatory protein (StAR)-related transfer (START) domain superfamily. In contrast to previous studies of proteins known to bind DNA-damaging natural products ( e.g ., bleomycins, mitomycins, and nine-membered chromoprotein enediynes), this is the first demonstrated involvement of a START domain fold. Consistent with the CalC self-sacrifice mechanism, CLM in complex with CalC is positioned for direct hydrogen abstraction from Gly113 to initiate the oxidative proteolysis-based resistance mechanism. These structural studies also illuminate, for the first time, a small DNA-binding region within CalC that may serve to localize CalC to the enediyne target (DNA). Given the role of START domains in nuclear/cytosolic transport and translocation, this structural study also may implicate START domains as post-endocytotic intracellular chaperones for enediyne-based therapeutics such as MyloTarg. | ||
==About this Structure== | ==About this Structure== | ||
1ZXF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Micromonospora_echinospora Micromonospora echinospora]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZXF OCA]. | 1ZXF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Micromonospora_echinospora Micromonospora echinospora]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZXF OCA]. | ||
| + | |||
| + | ==Reference== | ||
| + | Structural insight into the self-sacrifice mechanism of enediyne resistance., Singh S, Hager MH, Zhang C, Griffith BR, Lee MS, Hallenga K, Markley JL, Thorson JS, ACS Chem Biol. 2006 Aug 22;1(7):451-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17168523 17168523] | ||
[[Category: Micromonospora echinospora]] | [[Category: Micromonospora echinospora]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 31: | Line 37: | ||
[[Category: Self-sacrificing resistance protein]] | [[Category: Self-sacrificing resistance protein]] | ||
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | [[Category: Toxin]] |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 22 22:18:39 2008'' | ||
Revision as of 19:18, 22 May 2008
Solution structure of a self-sacrificing resistance protein, CalC from Micromonospora echinospora
Overview
The recent discovery of the first "self-sacrifice" mechanism for bacterial resistance to the enediyne antitumor antibiotics, where enediyne-induced proteolysis of the resistance protein CalC inactivates both the highly reactive metabolite and the resistance protein, revealed yet another ingenious bacterial mechanism for controlling reactive metabolites. As reported herein, the first 3D structures of CalC and CalC in complex with calicheamicin (CLM) divulge CalC to be a member of the steroidogenic acute regulatory protein (StAR)-related transfer (START) domain superfamily. In contrast to previous studies of proteins known to bind DNA-damaging natural products ( e.g ., bleomycins, mitomycins, and nine-membered chromoprotein enediynes), this is the first demonstrated involvement of a START domain fold. Consistent with the CalC self-sacrifice mechanism, CLM in complex with CalC is positioned for direct hydrogen abstraction from Gly113 to initiate the oxidative proteolysis-based resistance mechanism. These structural studies also illuminate, for the first time, a small DNA-binding region within CalC that may serve to localize CalC to the enediyne target (DNA). Given the role of START domains in nuclear/cytosolic transport and translocation, this structural study also may implicate START domains as post-endocytotic intracellular chaperones for enediyne-based therapeutics such as MyloTarg.
About this Structure
1ZXF is a Single protein structure of sequence from Micromonospora echinospora. Full crystallographic information is available from OCA.
Reference
Structural insight into the self-sacrifice mechanism of enediyne resistance., Singh S, Hager MH, Zhang C, Griffith BR, Lee MS, Hallenga K, Markley JL, Thorson JS, ACS Chem Biol. 2006 Aug 22;1(7):451-60. PMID:17168523 Page seeded by OCA on Thu May 22 22:18:39 2008
Categories: Micromonospora echinospora | Single protein | CESG, Center for Eukaryotic Structural Genomics. | Griffith, B R. | Hager, M H. | Hallenga, K. | Lee, M S. | Markley, J L. | Singh, S. | Thorson, J S. | Zhang, C. | Center for eukaryotic structural genomic | Cesg | Protein structure initiative | Psi | Self-sacrificing resistance protein | Structural genomic | Toxin
