|
|
| (13 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2q3n.gif|left|200px]] | |
| | | | |
| - | {{Structure
| + | ==Agglutinin from Abrus Precatorius (APA-I)== |
| - | |PDB= 2q3n |SIZE=350|CAPTION= <scene name='initialview01'>2q3n</scene>, resolution 3.50Å
| + | <StructureSection load='2q3n' size='340' side='right'caption='[[2q3n]], [[Resolution|resolution]] 3.50Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | + | <table><tr><td colspan='2'>[[2q3n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Abrus_precatorius Abrus precatorius]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2amz 2amz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q3N FirstGlance]. <br> |
| - | |ACTIVITY= [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]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> |
| - | |GENE= | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2q3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q3n OCA], [https://pdbe.org/2q3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q3n RCSB], [https://www.ebi.ac.uk/pdbsum/2q3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q3n ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AGGL_ABRPR AGGL_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 (By similarity). Less toxic than abrin-a.<ref>PMID:10636890</ref> [UniProtKB:P28590] The B chain is a galactose-specific lectin that facilitates the binding to the cell membrane that precedes endocytosis (By similarity).<ref>PMID:10636890</ref> [UniProtKB:P28590] |
| | + | == 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/q3/2q3n_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=2q3n ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate. |
| | | | |
| - | '''Agglutinin from Abrus Precatorius (APA-I)'''
| + | Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin.,Bagaria A, Surendranath K, Ramagopal UA, Ramakumar S, Karande AA J Biol Chem. 2006 Nov 10;281(45):34465-74. Epub 2006 Jun 13. PMID:16772301<ref>PMID:16772301</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2q3n" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate.
| + | *[[Agglutinin 3D structures|Agglutinin 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 2Q3N is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Abrus_precatorius Abrus precatorius]. This structure supersedes the now removed PDB entry 2AMZ. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3N OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin., Bagaria A, Surendranath K, Ramagopal UA, Ramakumar S, Karande AA, J Biol Chem. 2006 Nov 10;281(45):34465-74. Epub 2006 Jun 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16772301 16772301]
| + | |
| | [[Category: Abrus precatorius]] | | [[Category: Abrus precatorius]] |
| - | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| - | [[Category: rRNA N-glycosylase]]
| + | [[Category: Bagaria A]] |
| - | [[Category: Bagaria, A.]] | + | [[Category: Karande AA]] |
| - | [[Category: Karande, A A.]] | + | [[Category: Ramagopal UA]] |
| - | [[Category: Ramagopal, U A.]] | + | [[Category: Ramakumar S]] |
| - | [[Category: Ramakumar, S.]] | + | [[Category: Surendranath K]] |
| - | [[Category: Surendranath, K.]] | + | |
| - | [[Category: NAG]]
| + | |
| - | [[Category: agglutinin abrin]]
| + | |
| - | [[Category: immunotoxin]]
| + | |
| - | [[Category: ribosome-inactivating protein]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:21:13 2008''
| + | |
| Structural highlights
Function
AGGL_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 (By similarity). Less toxic than abrin-a.[1] [UniProtKB:P28590] The B chain is a galactose-specific lectin that facilitates the binding to the cell membrane that precedes endocytosis (By similarity).[2] [UniProtKB:P28590]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate.
Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin.,Bagaria A, Surendranath K, Ramagopal UA, Ramakumar S, Karande AA J Biol Chem. 2006 Nov 10;281(45):34465-74. Epub 2006 Jun 13. PMID:16772301[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu CL, Tsai CC, Lin SC, Wang LI, Hsu CI, Hwang MJ, Lin JY. Primary structure and function analysis of the Abrus precatorius agglutinin A chain by site-directed mutagenesis. Pro(199) Of amphiphilic alpha-helix H impairs protein synthesis inhibitory activity. J Biol Chem. 2000 Jan 21;275(3):1897-901. PMID:10636890
- ↑ Liu CL, Tsai CC, Lin SC, Wang LI, Hsu CI, Hwang MJ, Lin JY. Primary structure and function analysis of the Abrus precatorius agglutinin A chain by site-directed mutagenesis. Pro(199) Of amphiphilic alpha-helix H impairs protein synthesis inhibitory activity. J Biol Chem. 2000 Jan 21;275(3):1897-901. PMID:10636890
- ↑ Bagaria A, Surendranath K, Ramagopal UA, Ramakumar S, Karande AA. Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin. J Biol Chem. 2006 Nov 10;281(45):34465-74. Epub 2006 Jun 13. PMID:16772301 doi:http://dx.doi.org/10.1074/jbc.M601777200
|
