2aaz: 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: @@
-[[Image:2aaz.png|left|200px]]
-<!--
+==Cryptococcus neoformans thymidylate synthase complexed with substrate and an antifolate==
-The line below this paragraph, containing "STRUCTURE_2aaz", creates the "Structure Box" on the page.
+<StructureSection load='2aaz' size='340' side='right'caption='[[2aaz]], [[Resolution|resolution]] 2.08&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'>[[2aaz]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans Cryptococcus neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AAZ 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]] 2.08&#8491;, 4 models</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=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
-{{STRUCTURE_2aaz|  PDB=2aaz  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2aaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aaz OCA], [https://pdbe.org/2aaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aaz RCSB], [https://www.ebi.ac.uk/pdbsum/2aaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aaz ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TYSY_CRYNJ TYSY_CRYNJ]
+== 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/aa/2aaz_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=2aaz ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The ternary complex crystal structures of Cryptococcus neoformans and Escherichia coli thymidylate synthase (TS) suggest mechanisms of species-specific inhibition of a highly conserved protein. The 2.1 Angstrom structure of C. neoformans TS cocrystallized with substrate and the cofactor analog CB3717 shows that the binding sites for substrate and cofactor are highly conserved with respect to human TS, but that the structure of the cofactor-binding site of C. neoformans TS is less constrained by surrounding residues. This feature might allow C. neoformans TS to form TS-dUMP-inhibitor complexes with a greater range of antifolates than human TS. 3',3''-Dibromophenol-4-chloro-1,8-naphthalein (GA9) selectively inhibits both E. coli TS and C. neoformans TS (K(i) = 4 microM) over human TS (K(i) &gt;&gt; 245 microM). The E. coli TS-dUMP-GA9 complex is in an open conformation, similar to that of the apoenzyme crystal structure. The GA9-binding site overlaps the binding site of the pABA-glutamyl moiety of the cofactor. The fact that human apoTS can adopt an unusual fold in which the GA9-binding site is disordered may explain the poor affinity of GA9 for the human enzyme. These observations highlight the critical need to incorporate multiple target conformations in any computational attempt to facilitate drug discovery.
-===Cryptococcus neoformans thymidylate synthase complexed with substrate and an antifolate===
+The structure of Cryptococcus neoformans thymidylate synthase suggests strategies for using target dynamics for species-specific inhibition.,Finer-Moore JS, Anderson AC, O'Neil RH, Costi MP, Ferrari S, Krucinski J, Stroud RM Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1320-34. Epub 2005, Sep 28. PMID:16204883<ref>PMID:16204883</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2aaz" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16204883}}, adds the Publication Abstract to the page
+*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 16204883 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16204883}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Cryptococcus neoformans]]
-[[2aaz]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Filobasidiella_neoformans Filobasidiella neoformans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AAZ OCA].
+[[Category: Large Structures]]
+[[Category: Anderson AC]]
-==Reference==
+[[Category: Costi MP]]
-<ref group="xtra">PMID:16204883</ref><ref group="xtra">PMID:10377217</ref><ref group="xtra">PMID:9931028</ref><references group="xtra"/>
+[[Category: Ferrari S]]
-[[Category: Filobasidiella neoformans]]
+[[Category: Finer-Moore JS]]
-[[Category: Thymidylate synthase]]
+[[Category: Krucinski J]]
-[[Category: Anderson, A C.]]
+[[Category: O'Neil RH]]
-[[Category: Costi, M P.]]
+[[Category: Stroud RM]]
-[[Category: Ferrari, S.]]
-[[Category: Finer-Moore, J S.]]
-[[Category: Krucinski, J.]]
-[[Category: Neil, R H.O.]]
-[[Category: Stroud, R M.]]
-[[Category: Methyl transferase]]
-[[Category: Nucleotide biosynthesis]]
-[[Category: Transferase]]