4ffa: Difference between revisions
No edit summary |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Sulfatase from Mycobacterium tuberculosis== | ==Sulfatase from Mycobacterium tuberculosis== | ||
<StructureSection load='4ffa' size='340' side='right' caption='[[4ffa]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4ffa' size='340' side='right'caption='[[4ffa]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ffa]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4ffa]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FFA FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ffa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ffa OCA], [https://pdbe.org/4ffa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ffa RCSB], [https://www.ebi.ac.uk/pdbsum/4ffa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ffa ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/ATSK_MYCTU ATSK_MYCTU] Alpha-ketoglutarate-dependent sulfate ester dioxygenase, which oxidizes medium-chain alkyl-sulfate esters (PubMed:23762287). Shows preference for 2-ethylhexyl sulfate (2-EHS) in vitro, leading to the formation of succinate and 2-ethylhexanal (PubMed:23762287, PubMed:25427196). Has likely a role in sulfate scavenging in vivo (PubMed:23762287).<ref>PMID:23762287</ref> <ref>PMID:25427196</ref> Also causes the inactivation of the 2-carboxyquinoxaline Ty38c (an antitubercular compound that inhibits DprE1) via oxidative decarboxylation, using Ty38c instead of alpha-ketoglutarate as a substrate. Is thus responsible for primary resistance of M.tuberculosis to Ty38c in vitro. Overexpression of Rv3406 causes resistance to Ty38c.<ref>PMID:25427196</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 15: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4ffa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sulfatase 3D structures|Sulfatase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Bertozzi | [[Category: Bertozzi CR]] | ||
[[Category: Breidenbach | [[Category: Breidenbach MA]] | ||
[[Category: Gartner | [[Category: Gartner ZJ]] | ||
[[Category: Sogi | [[Category: Sogi KM]] | ||
Latest revision as of 13:51, 6 November 2024
Sulfatase from Mycobacterium tuberculosisSulfatase from Mycobacterium tuberculosis
Structural highlights
FunctionATSK_MYCTU Alpha-ketoglutarate-dependent sulfate ester dioxygenase, which oxidizes medium-chain alkyl-sulfate esters (PubMed:23762287). Shows preference for 2-ethylhexyl sulfate (2-EHS) in vitro, leading to the formation of succinate and 2-ethylhexanal (PubMed:23762287, PubMed:25427196). Has likely a role in sulfate scavenging in vivo (PubMed:23762287).[1] [2] Also causes the inactivation of the 2-carboxyquinoxaline Ty38c (an antitubercular compound that inhibits DprE1) via oxidative decarboxylation, using Ty38c instead of alpha-ketoglutarate as a substrate. Is thus responsible for primary resistance of M.tuberculosis to Ty38c in vitro. Overexpression of Rv3406 causes resistance to Ty38c.[3] Publication Abstract from PubMedThe genome of Mycobacterium tuberculosis (Mtb) encodes nine putative sulfatases, none of which have a known function or substrate. Here, we characterize Mtb's single putative type II sulfatase, Rv3406, as a non-heme iron (II) and alpha-ketoglutarate-dependent dioxygenase that catalyzes the oxidation and subsequent cleavage of alkyl sulfate esters. Rv3406 was identified based on its homology to the alkyl sulfatase AtsK from Pseudomonas putida. Using an in vitro biochemical assay, we confirmed that Rv3406 is a sulfatase with a preference for alkyl sulfate substrates similar to those processed by AtsK. We determined the crystal structure of the apo Rv3406 sulfatase at 2.5 A. The active site residues of Rv3406 and AtsK are essentially superimposable, suggesting that the two sulfatases share the same catalytic mechanism. Finally, we generated an Rv3406 mutant (Deltarv3406) in Mtb to study the sulfatase's role in sulfate scavenging. The Deltarv3406 strain did not replicate in minimal media with 2-ethyl hexyl sulfate as the sole sulfur source, in contrast to wild type Mtb or the complemented strain. We conclude that Rv3406 is an iron and alpha-ketoglutarate-dependent sulfate ester dioxygenase that has unique substrate specificity that is likely distinct from other Mtb sulfatases. Mycobacterium tuberculosis Rv3406 Is a Type II Alkyl Sulfatase Capable of Sulfate Scavenging.,Sogi KM, Gartner ZJ, Breidenbach MA, Appel MJ, Schelle MW, Bertozzi CR PLoS One. 2013 Jun 6;8(6):e65080. doi: 10.1371/journal.pone.0065080. Print 2013. PMID:23762287[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||