1il9: Difference between revisions

Revision as of 20:07, 2 May 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. 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 Fri May 2 20:07:28 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1il9.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1il9 |SIZE=350|CAPTION= <scene name='initialview01'>1il9</scene>, resolution 3.1&Aring;
+The line below this paragraph, containing "STRUCTURE_1il9", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=MOG:5-AMINO-2-METHYL-6H-OXAZOLO[5,4-D]PYRIMIDIN-7-ONE'>MOG</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1il9|  PDB=1il9  |  SCENE=  }}
-|RELATEDENTRY=[[1rtc|1RTC]], [[1br6|1BR6]], [[1br5|1BR5]], [[1fmp|1FMP]], [[1il3|1IL3]], [[1il4|1IL4]], [[1il5|1IL5]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1il9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1il9 OCA], [http://www.ebi.ac.uk/pdbsum/1il9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1il9 RCSB]</span>
-}}
 '''STRUCTURE OF RICIN A CHAIN BOUND WITH INHIBITOR 8-METHYL-9-OXOGUANINE'''
@@ Line 25: / Line 22: @@
 [[Category: Ricinus communis]]
 [[Category: Single protein]]
-[[Category: rRNA N-glycosylase]]
+[[Category: RRNA N-glycosylase]]
 [[Category: Kerwin, S M.]]
 [[Category: Miller, D J.]]
@@ Line 32: / Line 29: @@
 [[Category: Shen, H.]]
 [[Category: Suh, J K.]]
-[[Category: glycosidase]]
+[[Category: Glycosidase]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: ribosome-inhibiting protein]]
+[[Category: Ribosome-inhibiting protein]]
-[[Category: structure-based design]]
+[[Category: Structure-based design]]
-[[Category: toxin-inhibitor complex]]
+[[Category: Toxin-inhibitor complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 20:07:28 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:21:20 2008''