1ahc: Difference between revisions
New page: left|200px<br /><applet load="1ahc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ahc, resolution 2.0Å" /> '''THE N-GLYCOSIDASE MEC... |
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[[Image:1ahc.gif|left|200px]]<br /><applet load="1ahc" size=" | [[Image:1ahc.gif|left|200px]]<br /><applet load="1ahc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1ahc, resolution 2.0Å" /> | caption="1ahc, resolution 2.0Å" /> | ||
'''THE N-GLYCOSIDASE MECHANISM OF RIBOSOME-INACTIVATING PROTEINS IMPLIED BY CRYSTAL STRUCTURES OF ALPHA-MOMORCHARIN'''<br /> | '''THE N-GLYCOSIDASE MECHANISM OF RIBOSOME-INACTIVATING PROTEINS IMPLIED BY CRYSTAL STRUCTURES OF ALPHA-MOMORCHARIN'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: alpha-Momorcharin (alpha MMC) is a type I | BACKGROUND: alpha-Momorcharin (alpha MMC) is a type I ribosome-inactivating protein. It inhibits protein synthesis by hydrolytically removing a specific adenine residue from a highly conserved, single-stranded loop of rRNA. RESULTS: Here we describe the determination and refinement of the crystal structures of alpha MMC in the native state and in complexes with the product, adenine, and a substrate analogue, formycin 5'-monophosphate (FMP) at high resolution. Both adenine and the base of FMP are tightly bound; the ribose of bound FMP adopts a strained, high-energy conformation, which may mimic the structure of the transition state. CONCLUSIONS: These structures indicate that residues Tyr70, Glu160 and Arg163 of alpha MMC are the most critical for catalysis. We propose that the strained conformation of the ribose in the target adenosine weakens the glycoside bond. Partial protonation mediated by Arg163 then facilitates N-glycoside bond cleavage, leading to the formation of an oxycarbonium ion intermediate which is stabilized by the negatively-charged Glu160. Tyr70 adopts subtly different conformations in the three structures implying that it may be important in substrate recognition and perhaps catalysis. | ||
==About this Structure== | ==About this Structure== | ||
1AHC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Momordica_charantia Momordica charantia]. Active as [http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] Full crystallographic information is available from [http:// | 1AHC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Momordica_charantia Momordica charantia]. Active as [http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AHC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Dong, Y.]] | [[Category: Dong, Y.]] | ||
[[Category: Ren, J.]] | [[Category: Ren, J.]] | ||
[[Category: Stuart, D | [[Category: Stuart, D I.]] | ||
[[Category: Wang, Y.]] | [[Category: Wang, Y.]] | ||
[[Category: glycosidase]] | [[Category: glycosidase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:44:28 2008'' | ||
Revision as of 12:44, 21 February 2008
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THE N-GLYCOSIDASE MECHANISM OF RIBOSOME-INACTIVATING PROTEINS IMPLIED BY CRYSTAL STRUCTURES OF ALPHA-MOMORCHARIN
OverviewOverview
BACKGROUND: alpha-Momorcharin (alpha MMC) is a type I ribosome-inactivating protein. It inhibits protein synthesis by hydrolytically removing a specific adenine residue from a highly conserved, single-stranded loop of rRNA. RESULTS: Here we describe the determination and refinement of the crystal structures of alpha MMC in the native state and in complexes with the product, adenine, and a substrate analogue, formycin 5'-monophosphate (FMP) at high resolution. Both adenine and the base of FMP are tightly bound; the ribose of bound FMP adopts a strained, high-energy conformation, which may mimic the structure of the transition state. CONCLUSIONS: These structures indicate that residues Tyr70, Glu160 and Arg163 of alpha MMC are the most critical for catalysis. We propose that the strained conformation of the ribose in the target adenosine weakens the glycoside bond. Partial protonation mediated by Arg163 then facilitates N-glycoside bond cleavage, leading to the formation of an oxycarbonium ion intermediate which is stabilized by the negatively-charged Glu160. Tyr70 adopts subtly different conformations in the three structures implying that it may be important in substrate recognition and perhaps catalysis.
About this StructureAbout this Structure
1AHC is a Single protein structure of sequence from Momordica charantia. Active as rRNA N-glycosylase, with EC number 3.2.2.22 Full crystallographic information is available from OCA.
ReferenceReference
The N-glycosidase mechanism of ribosome-inactivating proteins implied by crystal structures of alpha-momorcharin., Ren J, Wang Y, Dong Y, Stuart DI, Structure. 1994 Jan 15;2(1):7-16. PMID:8075985
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