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[[Image:2r3d.jpg|left|200px]]<br /><applet load="2r3d" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2r3d, resolution 2.090&Aring;" />
'''Ricin A-chain (recombinant) complex with Acetamide'''<br />


==Overview==
==Ricin A-chain (recombinant) complex with Acetamide==
ABSTRACT: BACKGROUND: Ricin is a potent toxin and known bioterrorism, threat with no available antidote. The ricin A-chain (RTA) acts, enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship, between ligand binding and RTA active site conformational change, we used, a fragment-based approach to find a minimal set of bonding interactions, able to induce rearrangements in critical side-chain positions. RESULTS:, We found that the smallest ligand stabilizing an open conformer of the RTA, active site pocket was an amide group, bound weakly by only a few hydrogen, bonds to the protein. Complexes with small amide-containing molecules also, revealed a switch in geometry from a parallel towards a splayed, arrangement of an arginine-tryptophan cation-pi interaction that was, associated with an increase and red-shift in tryptophan fluorescence upon, ligand binding. Using the observed fluorescence signal, we determined the, thermodynamic changes of adenine binding to the RTA active site, as well, as the site-specific binding of urea. Urea binding had a favorable, enthalpy change and unfavorable entropy change, with a deltaH of -13 +/-2, kJ/mol and a deltaS of -0.04 +/-0.01 kJ/K*mol. The side-chain position of, residue Tyr80 in a complex with adenine was reexamined and found not to, involve as large an overlap of rings with the purine as previously, considered, suggesting a smaller role for aromatic stacking at the RTA, active site. CONCLUSIONS: We found that amide ligands can bind weakly but, specifically to the ricin active site, producing significant shifts in, positions of the critical active site residues Arg180 and Tyr80. These, results indicate that fragment-based drug discovery methods are capable of, identifying minimal bonding determinants of active-site side-chain, rearrangements and the mechanistic origins of spectroscopic shifts. Our, results suggest that tryptophan fluorescence provides a sensitive probe, for the geometric relationship of arginine-tryptophan pairs, which often, have significant roles in protein function. Using the unusual, characteristics of the RTA system, we measured the still controversial, thermodynamic changes of site-specific urea binding to a protein, results, that are relevant to understanding the physical mechanisms of protein, denaturation.
<StructureSection load='2r3d' size='340' side='right'caption='[[2r3d]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2r3d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1zb2 1zb2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R3D FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACM:ACETAMIDE'>ACM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2r3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r3d OCA], [https://pdbe.org/2r3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r3d RCSB], [https://www.ebi.ac.uk/pdbsum/2r3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r3d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RICI_RICCO RICI_RICCO] Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r3/2r3d_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2r3d ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2R3D 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=SO4:'>SO4</scene> and <scene name='pdbligand=ACM:'>ACM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1ZB2. 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=2R3D OCA].
*[[Ricin 3D structures|Ricin 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site., Carra JH, McHugh CA, Mulligan S, Machiesky LM, Soares AS, Millard CB, BMC Struct Biol. 2007 Nov 6;7(1):72. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17986339 17986339]
[[Category: Large Structures]]
[[Category: Ricinus communis]]
[[Category: Ricinus communis]]
[[Category: Single protein]]
[[Category: Carra JH]]
[[Category: rRNA N-glycosylase]]
[[Category: Machiesky LM]]
[[Category: Carra, J.H.]]
[[Category: McHugh CA]]
[[Category: Machiesky, L.M.]]
[[Category: Millard CB]]
[[Category: McHugh, C.A.]]
[[Category: Mulligan S]]
[[Category: Millard, C.B.]]
[[Category: Soares AS]]
[[Category: Mulligan, S.]]
[[Category: Soares, A.S.]]
[[Category: ACM]]
[[Category: SO4]]
[[Category: glycoprotein]]
[[Category: hydrolase]]
[[Category: lectin]]
[[Category: n-glycosidase]]
[[Category: plant defense]]
[[Category: protein synthesis inhibitor]]
[[Category: ricin]]
[[Category: ricinus communis]]
[[Category: toxin]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:10:14 2008''

Latest revision as of 12:19, 21 February 2024

Ricin A-chain (recombinant) complex with AcetamideRicin A-chain (recombinant) complex with Acetamide

Structural highlights

2r3d is a 1 chain structure with sequence from Ricinus communis. This structure supersedes the now removed PDB entry 1zb2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.09Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RICI_RICCO Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2r3d, resolution 2.09Å

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