2ql1

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (01:21, 21 November 2024) (edit) (undo)
 
(10 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:2ql1.png|left|200px]]
 
-
<!--
+
==Structural Characterization of a Mutated, ADCC-Enhanced Human Fc Fragment==
-
The line below this paragraph, containing "STRUCTURE_2ql1", creates the "Structure Box" on the page.
+
<StructureSection load='2ql1' size='340' side='right'caption='[[2ql1]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[2ql1]] is a 1 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=2QL1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QL1 FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.534&#8491;</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=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-
{{STRUCTURE_2ql1| PDB=2ql1 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ql1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ql1 OCA], [https://pdbe.org/2ql1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ql1 RCSB], [https://www.ebi.ac.uk/pdbsum/2ql1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ql1 ProSAT]</span></td></tr>
 +
</table>
 +
== 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 ==
 +
[[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/ql/2ql1_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2ql1 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
We report here the three-dimensional structure of a human Fc fragment engineered for enhanced antibody dependent cell mediated cytotoxicity (ADCC). The triple mutation S239D/A330L/I332E ('3M') was introduced into the C(H)2 portion of a human immunoglobulin G1 (IgG1) Fc. These three substitutions typically result in an about 10-100-fold increase in human IgG1 binding to human Fc gamma RIIIA (CD16). The recombinantly produced Fc/3M fragment was crystallized and its structure solved at a resolution of 2.5A using molecular replacement. No dramatic structural changes were observed in Fc/3M when compared with unmutated human Fc fragments. However, we found that the relative positions of its C(H)2 domains allowed for an unusually 'open' conformation of the entire fragment. Although this particular structural feature could be due to crystallization artifacts or intrinsic variability, we propose that molecular mechanisms at the basis of the enhanced interaction between Fc/3M and CD16 could include enhanced Fc openness as well as the introduction of additional hydrophobic contacts, hydrogen bonds and/or electrostatic interactions at the corresponding interface. The existence of a more pronounced cleft between the two Fc chains as well as of repulsive, electrostatic intra-chain interactions may also account in part for the decreased thermostability of both Fc/3M and a 3M-modified humanized anti-human EphA2 IgG1 when compared with their respective unmutated counterparts.
-
===Structural Characterization of a Mutated, ADCC-Enhanced Human Fc Fragment===
+
Structural characterization of a mutated, ADCC-enhanced human Fc fragment.,Oganesyan V, Damschroder MM, Leach W, Wu H, Dall'Acqua WF Mol Immunol. 2008 Apr;45(7):1872-82. PMID:18078997<ref>PMID:18078997</ref>
-
 
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<!--
+
</div>
-
The line below this paragraph, {{ABSTRACT_PUBMED_18078997}}, adds the Publication Abstract to the page
+
<div class="pdbe-citations 2ql1" style="background-color:#fffaf0;"></div>
-
(as it appears on PubMed at http://www.pubmed.gov), where 18078997 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_18078997}}
+
__TOC__
-
 
+
</StructureSection>
-
==Disease==
+
-
Known disease associated with this structure: Agammaglobulinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147020 147020]]
+
-
 
+
-
==About this Structure==
+
-
2QL1 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QL1 OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:18078997</ref><references group="xtra"/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Acqua, W F.Dall.]]
+
[[Category: Large Structures]]
-
[[Category: Oganesyan, V.]]
+
[[Category: Dall'Acqua WF]]
-
[[Category: Wu, H.]]
+
[[Category: Oganesyan V]]
-
[[Category: Adcc]]
+
[[Category: Wu H]]
-
[[Category: Antibody]]
+
-
[[Category: Crystal structure]]
+
-
[[Category: Fc fragment]]
+
-
[[Category: Immune system]]
+
-
[[Category: Mutation]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 14:56:17 2009''
+

Current revision

Structural Characterization of a Mutated, ADCC-Enhanced Human Fc Fragment

PDB ID 2ql1

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ql1"
Personal tools