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5z3j

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Crystal Structure of Abrin A chain (Recombinant) in complex with Nicotinamide at 1.7 Angstroms

Structural highlights

5z3j is a 1 chain structure with sequence from Abrus precatorius. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ABRA_ABRPR The A chain is responsible for inhibiting protein synthesis through the catalytic inactivation of 60S ribosomal subunits by removing adenine from position 4,324 of 28S rRNA. Abrin-a is more toxic than ricin. The B chain is a galactose-specific lectin that facilitates the binding of abrin to the cell membrane that precedes endocytosis.

Publication Abstract from PubMed

Abrin, an extremely cytotoxic Type-II ribosome inactivating protein (RIP), is a potential bio-warfare agent. Abrin A-chain (ABA) depurinates an adenosine of sarcin-ricin loop (SRL) from eukaryotic 28S rRNA thereby arresting protein synthesis and leading to cell death. Monoclonal antibody (mAb) D6F10 is the only known antibody that neutralizes ABA's activity in cell-free systems as well as abrin's toxicity in vitro and in vivo. However, how binding of mAb D6F10 to abrin interferes with abrin's catalytic activity at ribosome is still poorly understood. To provide structural basis for mAb D6F10-mediated rescue of ribosome inactivation by abrin, we determined crystal structures of ABA with and without substrate analogs. The structures of ABA-substrate analogs and ribosome were used in an experiment-guided computational protocol, to construct the ABA-Ribosome complex. A homology model of the variable region (Fv ) of mAb D6F10 was generated and docked with the apo-ABA structure to construct the ABA-D6F10 Fv complex. Structural superposition of ABA common to ABA-D6F10 Fv and ABA-Ribosome complexes reveals steric hindrance as the primary mechanism by which mAb D6F10 neutralizes abrin. In contrast to ABA alone, ABA bound to mAb D6F10 is unable to access the SRL on the ribosome owing to steric clashes of mAb D6F10 with the ribosome. Crystal structures of ABA also reveal a catalytic water molecule implicated in hydrolyzing N-glycosidic bond of the susceptible adenosine by RIPs. Furthermore, our strategy can be used to provide structural details of steric hindrance important for neutralization of ricin, another RIP, by mAb 6C2 and hence is of wide applicability. This article is protected by copyright. All rights reserved.

Structural basis for neutralization of cytotoxic abrin by monoclonal antibody D6F10.,Bansia H, Bagaria S, Karande AA, Ramakumar S FEBS J. 2018 Dec 6. doi: 10.1111/febs.14716. PMID:30521151^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bansia H, Bagaria S, Karande AA, Ramakumar S. Structural basis for neutralization of cytotoxic abrin by monoclonal antibody D6F10. FEBS J. 2018 Dec 6. doi: 10.1111/febs.14716. PMID:30521151 doi:http://dx.doi.org/10.1111/febs.14716

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5z3j"

Categories: Abrus precatorius | Large Structures | Bansia H | Karande AA | Ramakumar S

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Abrin A chain (Recombinant) in complex with Nicotinamide at 1.7 Angstroms==
-<StructureSection load='5z3j' size='340' side='right' caption='[[5z3j]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='5z3j' size='340' side='right'caption='[[5z3j]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5z3j]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z3J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z3J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5z3j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Abrus_precatorius Abrus precatorius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z3J FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5z3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z3j OCA], [http://pdbe.org/5z3j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z3j RCSB], [http://www.ebi.ac.uk/pdbsum/5z3j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z3j ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</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=5z3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z3j OCA], [https://pdbe.org/5z3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z3j RCSB], [https://www.ebi.ac.uk/pdbsum/5z3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z3j ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/ABRA_ABRPR ABRA_ABRPR] The A chain is responsible for inhibiting protein synthesis through the catalytic inactivation of 60S ribosomal subunits by removing adenine from position 4,324 of 28S rRNA. Abrin-a is more toxic than ricin.  The B chain is a galactose-specific lectin that facilitates the binding of abrin to the cell membrane that precedes endocytosis.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 19: @@
 </div>
 <div class="pdbe-citations 5z3j" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Abrin 3D structures|Abrin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bansia, H]]
+[[Category: Abrus precatorius]]
-[[Category: Karande, A A]]
+[[Category: Large Structures]]
-[[Category: Ramakumar, S]]
+[[Category: Bansia H]]
-[[Category: Hydrolase]]
+[[Category: Karande AA]]
-[[Category: Ribosome inactivating protein]]
+[[Category: Ramakumar S]]

5z3j

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Current revision

Crystal Structure of Abrin A chain (Recombinant) in complex with Nicotinamide at 1.7 Angstroms

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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