3d6g: Difference between revisions
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==Fc fragment of IgG1 (Herceptin) with protein-A mimetic peptide dendrimer ligand.== | ==Fc fragment of IgG1 (Herceptin) with protein-A mimetic peptide dendrimer ligand.== | ||
<StructureSection load='3d6g' size='340' side='right' caption='[[3d6g]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='3d6g' size='340' side='right'caption='[[3d6g]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3d6g]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3d6g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D6G FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=X12:2-[[(2~{S})-2,6-bis[[(2~{S})-2,6-bis[[(2~{R})-2-[[(2~{R},3~{R})-2-[[(2~{R})-2-azanyl-5-carbamimidamido-pentanoyl]amino]-3-oxidanyl-butanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]hexanoyl]amino]ethanoic+acid'>X12</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=3d6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d6g OCA], [https://pdbe.org/3d6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d6g RCSB], [https://www.ebi.ac.uk/pdbsum/3d6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d6g ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4. | ||
== Function == | |||
[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d6/3d6g_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d6/3d6g_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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=3d6g ConSurf]. | </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=3d6g ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Understanding the chemical physical properties of protein binding sites is at the basis of the rational design of protein ligands. The hinge region of the Fc fragment of immunoglobulin G is an important and well characterized protein binding site, known to interact with several natural proteins and synthetic ligands. Here, we report structural evidence that a Staphylococcus aureus Protein A mimetic peptide dendrimer, deduced by a combinatorial approach, binds close to the Cgamma2/Cgamma3 interface of the constant fragment of a human IgG1 molecule, partially hindering the Protein A binding site. The X-ray analysis evidenced a primary binding site located between a terminal Arg residue of the ligand peptidic arm and a hydrophobic protein site consisting of Val308, Leu309, and His310. A molecular dynamic analysis of the model derived from the X-ray structure showed that in water at room temperature the complex is further stabilized by the formation of at least one more contact between a terminal Arg residue of the second arm of the peptide and the carboxylic group of a protein amino acid, such as Glu318, Asp312, or Asp280. It appears thus that stability of the Fc-dendrimer complex is determined by the synergetic formation of multiple bonds of different nature between the dendrimer arms and the protein accessible sites. The electrostatic and van der Waals energies of the complex were monitored during the MD simulations and confirmed the energetic stability of the two interactions. | |||
Structural characterization of a Protein A mimetic peptide dendrimer bound to human IgG.,Moiani D, Salvalaglio M, Cavallotti C, Bujacz A, Redzynia I, Bujacz G, Dinon F, Pengo P, Fassina G J Phys Chem B. 2009 Dec 17;113(50):16268-75. doi: 10.1021/jp909405b. PMID:19924842<ref>PMID:19924842</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3d6g" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Bujacz | [[Category: Large Structures]] | ||
[[Category: Bujacz | [[Category: Bujacz AD]] | ||
[[Category: Dinon | [[Category: Bujacz GD]] | ||
[[Category: Fassina | [[Category: Dinon F]] | ||
[[Category: Pengo | [[Category: Fassina G]] | ||
[[Category: Redzynia | [[Category: Pengo P]] | ||
[[Category: Redzynia I]] | |||