This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3c6b

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:22, 30 August 2023) (edit) (undo)
 
(8 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3c6b.png|left|200px]]
 
-
<!--
+
==Reaction product of paraoxon and S-formylglutathione hydrolase W197I mutant==
-
The line below this paragraph, containing "STRUCTURE_3c6b", creates the "Structure Box" on the page.
+
<StructureSection load='3c6b' size='340' side='right'caption='[[3c6b]], [[Resolution|resolution]] 2.17&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'>[[3c6b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C6B 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]] 2.17&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SDP:2-AMINO-3-(DIETHOXY-PHOSPHORYLOXY)-PROPIONIC+ACID'>SDP</scene></td></tr>
-
{{STRUCTURE_3c6b| PDB=3c6b | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6b OCA], [https://pdbe.org/3c6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c6b RCSB], [https://www.ebi.ac.uk/pdbsum/3c6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c6b ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/SFGH_YEAST SFGH_YEAST] Serine hydrolase involved in the detoxification of formaldehyde.
 +
== 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/c6/3c6b_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=3c6b ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Saccharomyces cerevisiae expresses a 67.8 kDa homodimeric serine thioesterase, S-formylglutathione hydrolase (SFGH), that is 39.9% identical with human esterase D. Both enzymes possess significant carboxylesterase and S-formylglutathione thioesterase activity but are unusually resistant to organophosphate (OP) inhibitors. We determined the X-ray crystal structure of yeast (y) SFGH to 2.3 A resolution by multiwavelength anomalous dispersion and used the structure to guide site-specific mutagenesis experiments addressing substrate and inhibitor reactivity. Our results demonstrate a steric mechanism of OP resistance mediated by a single indole ring (W197) located in an enzyme "acyl pocket". The W197I substitution enhances ySFGH reactivity with paraoxon by &gt;1000-fold ( k i (W197I) = 16 +/- 2 mM (-1) h (-1)), thereby overcoming natural OP resistance. W197I increases the rate of OP inhibition under pseudo-first-order conditions but does not accelerate OP hydrolysis. The structure of the paraoxon-inhibited W197I variant was determined by molecular replacement (2.2 A); it revealed a stabilized sulfenic acid at Cys60. Wild-type (WT) ySFGH is inhibited by thiol reactive compounds and is sensitive to oxidation; thus, the cysteine sulfenic acid may play a role in the regulation of a "D-type" esterase. The structure of the W197I variant is the first reported cysteine sulfenic acid in a serine esterase. We constructed five Cys60/W197I variants and show that introducing a positive charge near the oxyanion hole, W197I/C60R or W197I/C60K, results in a further enhancement of the rates of phosphorylation with paraoxon ( k i = 42 or 80 mM (-1) h (-1), respectively) but does not affect the dephosphorylation of the enzyme. We also characterized three histidine substitutions near the oxyanion hole, G57H, L58H, and M162H, which significantly decrease esterase activity.
-
===Reaction product of paraoxon and S-formylglutathione hydrolase W197I mutant===
+
Structural characterization and reversal of the natural organophosphate resistance of a D-type esterase, Saccharomyces cerevisiae S-formylglutathione hydrolase.,Legler PM, Kumaran D, Swaminathan S, Studier FW, Millard CB Biochemistry. 2008 Sep 9;47(36):9592-601. Epub 2008 Aug 16. PMID:18707125<ref>PMID:18707125</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_18707125}}, adds the Publication Abstract to the page
+
<div class="pdbe-citations 3c6b" style="background-color:#fffaf0;"></div>
-
(as it appears on PubMed at http://www.pubmed.gov), where 18707125 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_18707125}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
[[Category: Large Structures]]
-
3C6B is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6B OCA].
+
-
 
+
-
==Reference==
+
-
Structural characterization and reversal of the natural organophosphate resistance of a D-type esterase, Saccharomyces cerevisiae S-formylglutathione hydrolase., Legler PM, Kumaran D, Swaminathan S, Studier FW, Millard CB, Biochemistry. 2008 Sep 9;47(36):9592-601. Epub 2008 Aug 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18707125 18707125]
+
-
[[Category: S-formylglutathione hydrolase]]
+
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
-
[[Category: Single protein]]
+
[[Category: Legler PM]]
-
[[Category: Legler, P M.]]
+
[[Category: Millard CB]]
-
[[Category: Millard, C B.]]
+
-
[[Category: Cysteine sulfenic acid]]
+
-
[[Category: Cytoplasm]]
+
-
[[Category: Formaldehyde]]
+
-
[[Category: Organophosphate]]
+
-
[[Category: Serine esterase]]
+
-
[[Category: Serine hydrolase]]
+
-
[[Category: Thioesterase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 22 09:50:47 2008''
+

Current revision

Reaction product of paraoxon and S-formylglutathione hydrolase W197I mutant

PDB ID 3c6b

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3c6b"
Personal tools