1il9: Difference between revisions
New page: left|200px<br /><applet load="1il9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1il9, resolution 3.1Å" /> '''STRUCTURE OF RICIN A ... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1il9.gif|left|200px]]<br /><applet load="1il9" size=" | [[Image:1il9.gif|left|200px]]<br /><applet load="1il9" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1il9, resolution 3.1Å" /> | caption="1il9, resolution 3.1Å" /> | ||
'''STRUCTURE OF RICIN A CHAIN BOUND WITH INHIBITOR 8-METHYL-9-OXOGUANINE'''<br /> | '''STRUCTURE OF RICIN A CHAIN BOUND WITH INHIBITOR 8-METHYL-9-OXOGUANINE'''<br /> | ||
==Overview== | ==Overview== | ||
Ribosome inhibiting proteins, RIPs, are a widespread family of toxic | Ribosome inhibiting proteins, RIPs, are a widespread family of toxic enzymes. Ricin is a plant toxin used as a poison and biological warfare agent; shiga toxin is a homologue expressed by pathogenic strains of E. coli. There is interest in creating effective antidote inhibitors to this class of enzymes. RIPs act by binding and hydrolyzing a specific adenine base from rRNA. Previous virtual screens revealed that pterins could bind in the specificity pocket of ricin and inhibit the enzyme. In this paper we explore a range of compounds that could serve as better platforms for inhibitor design. This establishes the importance of key hydrogen bond donors and acceptors for active-site complementarity. 8-Methyl-9-oxoguanine is a soluble compound that has the best inhibitory properties of any platform tested. The X-ray structure of this complex revealed that the inhibitor binds in an unexpected way that provides insight for future design. Several inhibitors of ricin were also shown to be inhibitors of shiga toxin, suggesting this program has the potential to develop effective antidotes to an important form of food poisoning. | ||
==About this Structure== | ==About this Structure== | ||
1IL9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis] with MOG as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | 1IL9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis] with <scene name='pdbligand=MOG:'>MOG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1IL9 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: rRNA N-glycosylase]] | [[Category: rRNA N-glycosylase]] | ||
[[Category: Kerwin, S | [[Category: Kerwin, S M.]] | ||
[[Category: Miller, D | [[Category: Miller, D J.]] | ||
[[Category: Ravikumar, K.]] | [[Category: Ravikumar, K.]] | ||
[[Category: Robertus, J | [[Category: Robertus, J D.]] | ||
[[Category: Shen, H.]] | [[Category: Shen, H.]] | ||
[[Category: Suh, J | [[Category: Suh, J K.]] | ||
[[Category: MOG]] | [[Category: MOG]] | ||
[[Category: glycosidase]] | [[Category: glycosidase]] | ||
| Line 27: | Line 27: | ||
[[Category: toxin-inhibitor complex]] | [[Category: toxin-inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:13:04 2008'' | ||
Revision as of 14:13, 21 February 2008
|
STRUCTURE OF RICIN A CHAIN BOUND WITH INHIBITOR 8-METHYL-9-OXOGUANINE
OverviewOverview
Ribosome inhibiting proteins, RIPs, are a widespread family of toxic enzymes. Ricin is a plant toxin used as a poison and biological warfare agent; shiga toxin is a homologue expressed by pathogenic strains of E. coli. There is interest in creating effective antidote inhibitors to this class of enzymes. RIPs act by binding and hydrolyzing a specific adenine base from rRNA. Previous virtual screens revealed that pterins could bind in the specificity pocket of ricin and inhibit the enzyme. In this paper we explore a range of compounds that could serve as better platforms for inhibitor design. This establishes the importance of key hydrogen bond donors and acceptors for active-site complementarity. 8-Methyl-9-oxoguanine is a soluble compound that has the best inhibitory properties of any platform tested. The X-ray structure of this complex revealed that the inhibitor binds in an unexpected way that provides insight for future design. Several inhibitors of ricin were also shown to be inhibitors of shiga toxin, suggesting this program has the potential to develop effective antidotes to an important form of food poisoning.
About this StructureAbout this Structure
1IL9 is a Single protein structure of sequence from Ricinus communis with as ligand. Active as rRNA N-glycosylase, with EC number 3.2.2.22 Full crystallographic information is available from OCA.
ReferenceReference
Structure-based design and characterization of novel platforms for ricin and shiga toxin inhibition., Miller DJ, Ravikumar K, Shen H, Suh JK, Kerwin SM, Robertus JD, J Med Chem. 2002 Jan 3;45(1):90-8. PMID:11754581
Page seeded by OCA on Thu Feb 21 13:13:04 2008