3gb6: Difference between revisions

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-{{Seed}}
-[[Image:3gb6.png|left|200px]]
-<!--
+==Structure of Giardia fructose-1,6-biphosphate aldolase D83A mutant in complex with fructose-1,6-bisphosphate==
-The line below this paragraph, containing "STRUCTURE_3gb6", creates the "Structure Box" on the page.
+<StructureSection load='3gb6' size='340' side='right'caption='[[3gb6]], [[Resolution|resolution]] 2.00&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'>[[3gb6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Giardia_intestinalis Giardia intestinalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GB6 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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P6F:1,6-DI-O-PHOSPHONO-D-FRUCTOSE'>P6F</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3gb6|  PDB=3gb6  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gb6 OCA], [https://pdbe.org/3gb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gb6 RCSB], [https://www.ebi.ac.uk/pdbsum/3gb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gb6 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A8B2U2_GIAIC A8B2U2_GIAIC]
+== 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/gb/3gb6_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=3gb6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Giardia lamblia fructose-1,6-bisphosphate aldolase (FBPA) is a member of the class II zinc-dependent aldolase family that catalyzes the cleavage of d-fructose 1,6-bisphosphate (FBP) into dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate (G3P). In addition to the active site zinc, the catalytic apparatus of FBPA employs an aspartic acid, Asp83 in the G. lamblia enzyme, which when replaced with an alanine residue renders the enzyme inactive. A comparison of the crystal structures of D83A FBPA in complex with FBP and of wild-type FBPA in the unbound state revealed a substrate-induced conformational transition of loops in the vicinity of the active site and a shift in the location of Zn(2+). When FBP binds, the Zn(2+) shifts up to 4.6 A toward the catalytic Asp83, which brings the metal within coordination distance of the Asp83 carboxylate group. In addition, the structure of wild-type FBPA was determined in complex with the competitive inhibitor d-tagatose 1,6-bisphosphate (TBP), a FBP stereoisomer. In this structure, the zinc binds in a site close to that previously seen in the structure of FBPA in complex with phosphoglycolohydroxamate, an analogue of the postulated DHAP ene-diolate intermediate. Together, the ensemble of structures suggests that the zinc mobility is necessary to orient the Asp83 side chain and to polarize the substrate for proton transfer from the FBP C(4) hydroxyl group to the Asp83 carboxyl group. In the absence of FBP, the alternative zinc position is too remote for coordinating the Asp83. We propose a modification of the catalytic mechanism that incorporates the novel features observed in the FBPA-FBP structure. The mechanism invokes coordination and coplanarity of the Zn(2+) with the FBP's O-C(3)-C(4)-O group concomitant with coordination of the Asp83 carboxylic group. Catalysis is accompanied by movement of Zn(2+) to a site coplanar with the O-C(2)-C(3)-O group of the DHAP. glFBPA exhibits strict substrate specificity toward FBP and does not cleave TBP. The active sites of FBPAs contain an aspartate residue equivalent to Asp255 of glFBPA, whereas tagatose-1,6-bisphosphate aldolase contains an alanine in this position. We and others hypothesized that this aspartic acid is a likely determinant of FBP versus TBP specificity. Replacement of Asp255 with an alanine resulted in an enzyme that possesses double specificity, now cleaving TBP (albeit with low efficacy; k(cat)/K(m) = 80 M(-1) s(-1)) while maintaining activity toward FBP at a 50-fold lower catalytic efficacy compared with that of wild-type FBPA. The collection of structures and sequence analyses highlighted additional residues that may be involved in substrate discrimination.
-===Structure of Giardia fructose-1,6-biphosphate aldolase D83A mutant in complex with fructose-1,6-bisphosphate===
+Structural Insights into the Substrate Binding and Stereoselectivity of Giardia Fructose-1,6-bisphosphate Aldolase (dagger) (,) (double dagger).,Galkin A, Li Z, Li L, Kulakova L, Pal LR, Dunaway-Mariano D, Herzberg O Biochemistry. 2009 Mar 18. PMID:19236002<ref>PMID:19236002</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3gb6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19236002}}, adds the Publication Abstract to the page
+*[[Aldolase 3D structures|Aldolase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19236002 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19236002}}
+__TOC__
+</StructureSection>
-==About this Structure==
-GB6 is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Giardia_intestinalis Giardia intestinalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GB6 OCA].
-==Reference==
-<ref group="xtra">PMID:19236002</ref><references group="xtra"/>
-[[Category: Fructose-bisphosphate aldolase]]
 [[Category: Giardia intestinalis]]
-[[Category: Galkin, A.]]
+[[Category: Large Structures]]
-[[Category: Herzberg, O.]]
+[[Category: Galkin A]]
-[[Category: 6-bisphosphate aldolase]]
+[[Category: Herzberg O]]
-[[Category: Class ii fructose-1]]
-[[Category: Drug target]]
-[[Category: Giardia lamblia]]
-[[Category: Glycolysis]]
-[[Category: Glycolytic pathway]]
-[[Category: Lyase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 10 10:48:54 2010''