3dl6: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3dl6.png|left|200px]]
-<!--
+==Crystal Structure of the A287F/S290G Active Site Mutant of TS-DHFR from Cryptosporidium hominis==
-The line below this paragraph, containing "STRUCTURE_3dl6", creates the "Structure Box" on the page.
+<StructureSection load='3dl6' size='340' side='right'caption='[[3dl6]], [[Resolution|resolution]] 3.25&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'>[[3dl6]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_hominis Cryptosporidium hominis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DL6 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]] 3.25&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=DHF:DIHYDROFOLIC+ACID'>DHF</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
-{{STRUCTURE_3dl6|  PDB=3dl6  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dl6 OCA], [https://pdbe.org/3dl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dl6 RCSB], [https://www.ebi.ac.uk/pdbsum/3dl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dl6 ProSAT]</span></td></tr>
+</table>
+== 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/dl/3dl6_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=3dl6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The essential enzyme TS-DHFR from Cryptosporidium hominis undergoes an unusually rapid rate of catalysis at the conserved TS domain, facilitated by two nonconserved residues, Ala287 and Ser290, in the folate tail-binding region. Mutation of these two residues to their conserved counterparts drastically affects multiple steps of the TS catalytic cycle. We have determined the crystal structures of all three mutants (A287F, S290G, and A287F/S290G) in complex with active site ligands dUMP and CB3717. The structural data show two effects of the mutations: an increased distance between the ligands in the active site and increased flexibility of the folate ligand in the partially open enzyme state that precedes conformational change to the active catalytic state. The latter effect is able to be rescued by the mutants containing the A287F mutation. In addition, the conserved water network of TS is altered in each of the mutants. The structural results point to a role of the folate tail-binding residues in closely positioning ChTS ligands and restricting ligand flexibility in the partially open state to allow for a rapid transition to the active closed state and enhanced rate of catalysis. These results provide an explanation on how folate tail-binding residues at one end of the active site affect long-range interactions throughout the TS active site and validate these residues as targets for species-specific drug design.
-===Crystal Structure of the A287F/S290G Active Site Mutant of TS-DHFR from Cryptosporidium hominis===
+Explaining an unusually fast parasitic enzyme: folate tail-binding residues dictate substrate positioning and catalysis in Cryptosporidium hominis thymidylate synthase.,Martucci WE, Vargo MA, Anderson KS Biochemistry. 2008 Aug 26;47(34):8902-11. Epub 2008 Aug 2. PMID:18672899<ref>PMID:18672899</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3dl6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18672899}}, adds the Publication Abstract to the page
+*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18672899 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_18672899}}
+__TOC__
+</StructureSection>
-==About this Structure==
-DL6 is a 5 chains structure of sequences from [http://en.wikipedia.org/wiki/Cryptosporidium_hominis Cryptosporidium hominis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DL6 OCA].
-==Reference==
-<ref group="xtra">PMID:18672899</ref><references group="xtra"/>
 [[Category: Cryptosporidium hominis]]
-[[Category: Dihydrofolate reductase]]
+[[Category: Large Structures]]
-[[Category: Anderson, K S.]]
+[[Category: Anderson KS]]
-[[Category: Martucci, W E.]]
+[[Category: Martucci WE]]
-[[Category: Vargo, M A.]]
+[[Category: Vargo MA]]
-[[Category: Enzyme active site mutant]]
-[[Category: Enzyme-ligand complex]]
-[[Category: Oxidoreductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 09:53:37 2009''