2dqt: Difference between revisions

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-[[Image:2dqt.png|left|200px]]
-<!--
+==High resolution crystal structure of the complex of the hydrolytic antibody Fab 6D9 and a transition-state analog==
-The line below this paragraph, containing "STRUCTURE_2dqt", creates the "Structure Box" on the page.
+<StructureSection load='2dqt' size='340' side='right'caption='[[2dqt]], [[Resolution|resolution]] 1.80&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'>[[2dqt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1hyx 1hyx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DQT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DQT 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]] 1.8&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPD:[1-(3-DIMETHYLAMINO-PROPYL)-3-ETHYL-UREIDO]-[4-(2,2,2-TRIFLUORO-ACETYLAMINO)-BENZYL]PHOSPHINIC+ACID-2-(2,2-DIHYDRO-ACETYLAMINO)-3-HYDROXY-1-(4-NITROPHENYL)-PROPYL+ESTER'>CPD</scene></td></tr>
-{{STRUCTURE_2dqt|  PDB=2dqt  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2dqt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dqt OCA], [https://pdbe.org/2dqt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dqt RCSB], [https://www.ebi.ac.uk/pdbsum/2dqt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dqt ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A2NHM3_MOUSE A2NHM3_MOUSE]
+== 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/dq/2dqt_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=2dqt ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Catalytic antibodies 6D9 and 9C10, which were induced by immunization with a haptenic transition-state analog (TSA), catalyze the hydrolysis of a nonbioactive chloramphenicol monoester derivative to generate a bioactive chloramphenicol. These antibodies stabilize the transition state to catalyze the hydrolysis reaction, strictly according to the theoretical relationship: for 6D9, k(cat)/k(uncat)=895 and K(S)/K(TSA)=900, and for 9C10, k(cat)/k(uncat)=56 and K(S)/K(TSA)=60. To elucidate the molecular basis of the antibody-catalyzed reaction, the crystal structure of 6D9 was determined, and the binding thermodynamics of 6D9 and 9C10 with both the substrate and the TSA were analyzed using isothermal titration calorimetry. The crystal structure of the unliganded 6D9 Fab was determined at 2.25 A resolution and compared with that of the TSA-liganded 6D9 Fab reported previously, showing that the TSA is bound into the hydrophobic pocket of the antigen-combining site in an "induced fit" manner, especially at the L1 and H3 CDR loops. Thermodynamic analyses showed that 6D9 binds the substrate of the TSA with a positive DeltaS, differing from general thermodynamic characteristics of antigen-antibody interactions. This positive DeltaS could be due to the hydrophobic interactions between 6D9 and the substrate or the TSA mediated by Trp H100i. The difference in DeltaG between substrate and TSA-binding to 6D9 was larger than that to 9C10, which is in good correlation with the larger k(cat) value of 6D9. Interestingly, the DeltaDeltaG was mainly because of the DeltaDeltaH. The correlation between k(cat) and DeltaDeltaH is suggestive of "enthalpic strain" leading to destabilization of antibody-substrate complexes. Together with X-ray structural analyses, the thermodynamic analyses suggest that upon binding the substrate, the antibody alters the conformation of the ester moiety in the substrate from the planar Z form to a thermodynamically unstable twisted conformation, followed by conversion into the transition state. Enthalpic strain also contributes to the transition-state stabilization by destabilizing the ground state, and its degree is much larger for the more efficient catalytic antibody, 6D9.
-===High resolution crystal structure of the complex of the hydrolytic antibody Fab 6D9 and a transition-state analog===
+Thermodynamic and structural basis for transition-state stabilization in antibody-catalyzed hydrolysis.,Oda M, Ito N, Tsumuraya T, Suzuki K, Sakakura M, Fujii I J Mol Biol. 2007 May 25;369(1):198-209. Epub 2007 Mar 15. PMID:17428500<ref>PMID:17428500</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2dqt" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17428500}}, adds the Publication Abstract to the page
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17428500 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17428500}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-[[2dqt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1hyx 1hyx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DQT OCA].
-==Reference==
-<ref group="xtra">PMID:17428500</ref><ref group="xtra">PMID:9150409</ref><ref group="xtra">PMID:7938025</ref><ref group="xtra">PMID:8016113</ref><ref group="xtra">PMID:8506382</ref><references group="xtra"/>
 [[Category: Mus musculus]]
-[[Category: Fujii, I.]]
+[[Category: Fujii I]]
-[[Category: Ito, N.]]
+[[Category: Ito N]]
-[[Category: Kristensen, O.]]
+[[Category: Kristensen O]]
-[[Category: Morikawa, K.]]
+[[Category: Morikawa K]]
-[[Category: Tanaka, F.]]
+[[Category: Tanaka F]]
-[[Category: Vassylyev, D G.]]
+[[Category: Vassylyev DG]]
-[[Category: Catalytic antibody]]
-[[Category: Ester hydrolysis]]
-[[Category: Esterolytic]]
-[[Category: Fab]]
-[[Category: Immune system]]
-[[Category: Immunoglobulin]]