4a5o: 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:4a5o.png|left|200px]]
-<!--
+==Crystal structure of Pseudomonas aeruginosa N5, N10- methylenetetrahydrofolate dehydrogenase-cyclohydrolase (FolD)==
-The line below this paragraph, containing "STRUCTURE_4a5o", creates the "Structure Box" on the page.
+<StructureSection load='4a5o' size='340' side='right'caption='[[4a5o]], [[Resolution|resolution]] 2.20&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'>[[4a5o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A5O 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]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-{{STRUCTURE_4a5o|  PDB=4a5o  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5o OCA], [https://pdbe.org/4a5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a5o RCSB], [https://www.ebi.ac.uk/pdbsum/4a5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a5o ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FOLD_PSEAE FOLD_PSEAE] Catalyzes the oxidation of 5,10-methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate.<ref>PMID:22558288</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The bifunctional enzyme methylenetetrahydrofolate dehydrogenase - cyclohydrolase (FolD) is identified as a potential drug target in Gram-negative bacteria, in particular the troublesome Pseudomonas aeruginosa. In order to provide a comprehensive and realistic assessment of the potential of this target for drug discovery we generated a highly efficient recombinant protein production system and purification protocol, characterized the enzyme, carried out screening of two commercial compound libraries by differential scanning fluorimetry, developed a high-throughput enzyme assay and prosecuted a screening campaign against almost 80,000 compounds. The crystal structure of P. aeruginosa FolD was determined at 2.2 A resolution and provided a template for an assessment of druggability and for modelling of ligand complexes as well as for comparisons with the human enzyme. New FolD inhibitors were identified and characterized but the weak levels of enzyme inhibition suggest that these compounds are not optimal starting points for future development. Furthermore, the close similarity of the bacterial and human enzyme structures suggest that selective inhibition might be difficult to attain. In conclusion, although the preliminary biological data indicates that FolD represents a valuable target for the development of new antibacterial drugs, indeed spurred us to investigate it, our screening results and structural data suggest that this would be a difficult enzyme to target with respect to developing the appropriate lead molecules required to underpin a serious drug discovery effort.
-===Crystal structure of Pseudomonas aeruginosa N5, N10- methylenetetrahydrofolate dehydrogenase-cyclohydrolase (FolD)===
+Assessment of Pseudomonas aeruginosa N(5),N(10)-Methylenetetrahydrofolate Dehydrogenase - Cyclohydrolase as a Potential Antibacterial Drug Target.,Eadsforth TC, Gardiner M, Maluf FV, McElroy S, James D, Frearson J, Gray D, Hunter WN PLoS One. 2012;7(4):e35973. Epub 2012 Apr 25. PMID:22558288<ref>PMID:22558288</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_22558288}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 4a5o" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 22558288 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22558288}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-[[4a5o]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_pao1 Pseudomonas aeruginosa pao1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A5O OCA].
+[[Category: Pseudomonas aeruginosa PAO1]]
+[[Category: Eadsforth TC]]
-==Reference==
+[[Category: Frearson J]]
-<ref group="xtra">PMID:022558288</ref><references group="xtra"/>
+[[Category: Gardiner M]]
-[[Category: Pseudomonas aeruginosa pao1]]
+[[Category: Gray D]]
-[[Category: Eadsforth, T C.]]
+[[Category: Hunter WN]]
-[[Category: Frearson, J.]]
+[[Category: James D]]
-[[Category: Gardiner, M.]]
+[[Category: Maluf FV]]
-[[Category: Gray, D.]]
+[[Category: McElroy S]]
-[[Category: Hunter, W N.]]
-[[Category: James, D.]]
-[[Category: Maluf, F V.]]
-[[Category: Mcelroy, S.]]
-[[Category: Hydrolase]]
-[[Category: Oxidoreductase]]