1g6v: Difference between revisions

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-[[Image:1g6v.gif|left|200px]]<br />
-<applet load="1g6v" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1g6v, resolution 3.5&Aring;" />
-'''Complex of the camelid heavy-chain antibody fragment CAB-CA05 with bovine carbonic anhydrase'''<br />
-==Overview==
+==Complex of the camelid heavy-chain antibody fragment CAB-CA05 with bovine carbonic anhydrase==
-Detailed knowledge on antibody-antigen recognition is scarce given the, unlimited antibody specificities of which only few have been investigated, at an atomic level. We report the crystal structures of an antibody, fragment derived from a camel heavy chain antibody against carbonic, anhydrase, free and in complex with antigen. Surprisingly, this, single-domain antibody interacts with nanomolar affinity with the antigen, through its third hypervariable loop (19 amino acids long), providing a, flat interacting surface of 620 A(2). For the first time, a single-domain, antibody is observed with its first hypervariable loop adopting a type-1, canonical structure. The second hypervariable loop, of unique size due to, a somatic mutation, reveals a regular beta-turn. The third hypervariable, loop covers the remaining hypervariable loops and the side of the domain, that normally interacts with the variable domain of the light chain., Specific amino acid substitutions and reoriented side chains reshape this, side of the domain and increase its hydrophilicity. Of interest is the, substitution of the conserved Trp-103 by Arg because it opens new, perspectives to 'humanize' a camel variable domain of heavy chain of heavy, chain antibody (VHH) or to 'camelize' a human or a mouse variable domain, of heavy chain of conventional antibody (VH).
+<StructureSection load='1g6v' size='340' side='right'caption='[[1g6v]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1g6v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G6V 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]] 3.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1g6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g6v OCA], [https://pdbe.org/1g6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g6v RCSB], [https://www.ebi.ac.uk/pdbsum/1g6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g6v ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CAH2_BOVIN CAH2_BOVIN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide.
+== 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/g6/1g6v_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=1g6v ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Detailed knowledge on antibody-antigen recognition is scarce given the unlimited antibody specificities of which only few have been investigated at an atomic level. We report the crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen. Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third hypervariable loop (19 amino acids long), providing a flat interacting surface of 620 A(2). For the first time, a single-domain antibody is observed with its first hypervariable loop adopting a type-1 canonical structure. The second hypervariable loop, of unique size due to a somatic mutation, reveals a regular beta-turn. The third hypervariable loop covers the remaining hypervariable loops and the side of the domain that normally interacts with the variable domain of the light chain. Specific amino acid substitutions and reoriented side chains reshape this side of the domain and increase its hydrophilicity. Of interest is the substitution of the conserved Trp-103 by Arg because it opens new perspectives to 'humanize' a camel variable domain of heavy chain of heavy chain antibody (VHH) or to 'camelize' a human or a mouse variable domain of heavy chain of conventional antibody (VH).
-==About this Structure==
+Antigen specificity and high affinity binding provided by one single loop of a camel single-domain antibody.,Desmyter A, Decanniere K, Muyldermans S, Wyns L J Biol Chem. 2001 Jul 13;276(28):26285-90. Epub 2001 May 7. PMID:11342547<ref>PMID:11342547</ref>
-G6V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1G6V OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Antigen specificity and high affinity binding provided by one single loop of a camel single-domain antibody., Desmyter A, Decanniere K, Muyldermans S, Wyns L, J Biol Chem. 2001 Jul 13;276(28):26285-90. Epub 2001 May 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11342547 11342547]
+</div>
+<div class="pdbe-citations 1g6v" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
 [[Category: Camelus dromedarius]]
-[[Category: Carbonate dehydratase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Decanniere K]]
-[[Category: Decanniere, K.]]
+[[Category: Desmyter A]]
-[[Category: Desmyter, A.]]
+[[Category: Muyldermans S]]
-[[Category: Muyldermans, S.]]
+[[Category: Wyns L]]
-[[Category: Wyns, L.]]
-[[Category: ZN]]
-[[Category: antibody]]
-[[Category: antigen]]
-[[Category: complex]]
-[[Category: immunoglobulin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:30:52 2007''