6eci: Difference between revisions
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<StructureSection load='6eci' size='340' side='right' caption='[[6eci]], [[Resolution|resolution]] 2.69Å' scene=''> | <StructureSection load='6eci' size='340' side='right' caption='[[6eci]], [[Resolution|resolution]] 2.69Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6eci]] is a 20 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ECI FirstGlance]. <br> | <table><tr><td colspan='2'>[[6eci]] is a 20 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ECI FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSMEI_5105 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6eci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eci OCA], [http://pdbe.org/6eci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eci RCSB], [http://www.ebi.ac.uk/pdbsum/6eci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eci ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6eci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eci OCA], [http://pdbe.org/6eci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eci RCSB], [http://www.ebi.ac.uk/pdbsum/6eci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eci ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ability to persist in the absence of growth triggered by low-oxygen levels is a critical process for the survival of mycobacterial species in many environmental niches. MSMEG_5243 (fsq), a gene of unknown function in Mycobacterium smegmatis, is up-regulated in response to hypoxia and regulated by DosRDosS/DosT, an oxygen- and redox-sensing two-component system that is highly conserved in mycobacteria. In this communication, we demonstrate that MSMEG_5243 is a flavin-sequestering protein and henceforth refer to it as Fsq. Using an array of biochemical and structural analyses, we show that Fsq is a member of the diverse superfamily of flavin- and deazaflavin-dependent oxidoreductases (FDORs) and is widely distributed in mycobacterial species. We created a markerless deletion mutant of fsq and demonstrate that fsqis required for cell survival during hypoxia. Using fsq deletion and overexpression, we found that fsq enhances cellular resistance to hydrogen peroxide treatment. The X-ray crystal structure of Fsq, solved to 2.7 A, revealed a homodimeric organization with FAD bound noncovalently. The Fsq structure also uncovered no potential substrate-binding cavities, as the FAD is fully enclosed, and electrochemical studies indicated that the Fsq:FAD complex is relatively inert and does not share common properties with electron-transfer proteins. Taken together, our results suggest that Fsq reduces the formation of reactive oxygen species (ROS) by sequestering free FAD during recovery from hypoxia, thereby protecting the cofactor from undergoing autoxidation to produce ROS. This finding represents a new paradigm in mycobacterial adaptation to hypoxia. | |||
FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress.,Harold LK, Antoney J, Ahmed FH, Hards K, Carr PD, Rapson T, Greening C, Jackson CJ, Cook GM J Biol Chem. 2018 Dec 19. pii: RA118.006237. doi: 10.1074/jbc.RA118.006237. PMID:30567740<ref>PMID:30567740</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6eci" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Mycs2]] | |||
[[Category: Ahmed, F H]] | [[Category: Ahmed, F H]] | ||
[[Category: Antoney, J]] | [[Category: Antoney, J]] | ||
Revision as of 15:32, 16 January 2019
Structure of the FAD binding protein MSMEG_5243 from Mycobacterium smegmatisStructure of the FAD binding protein MSMEG_5243 from Mycobacterium smegmatis
Structural highlights
Publication Abstract from PubMedThe ability to persist in the absence of growth triggered by low-oxygen levels is a critical process for the survival of mycobacterial species in many environmental niches. MSMEG_5243 (fsq), a gene of unknown function in Mycobacterium smegmatis, is up-regulated in response to hypoxia and regulated by DosRDosS/DosT, an oxygen- and redox-sensing two-component system that is highly conserved in mycobacteria. In this communication, we demonstrate that MSMEG_5243 is a flavin-sequestering protein and henceforth refer to it as Fsq. Using an array of biochemical and structural analyses, we show that Fsq is a member of the diverse superfamily of flavin- and deazaflavin-dependent oxidoreductases (FDORs) and is widely distributed in mycobacterial species. We created a markerless deletion mutant of fsq and demonstrate that fsqis required for cell survival during hypoxia. Using fsq deletion and overexpression, we found that fsq enhances cellular resistance to hydrogen peroxide treatment. The X-ray crystal structure of Fsq, solved to 2.7 A, revealed a homodimeric organization with FAD bound noncovalently. The Fsq structure also uncovered no potential substrate-binding cavities, as the FAD is fully enclosed, and electrochemical studies indicated that the Fsq:FAD complex is relatively inert and does not share common properties with electron-transfer proteins. Taken together, our results suggest that Fsq reduces the formation of reactive oxygen species (ROS) by sequestering free FAD during recovery from hypoxia, thereby protecting the cofactor from undergoing autoxidation to produce ROS. This finding represents a new paradigm in mycobacterial adaptation to hypoxia. FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress.,Harold LK, Antoney J, Ahmed FH, Hards K, Carr PD, Rapson T, Greening C, Jackson CJ, Cook GM J Biol Chem. 2018 Dec 19. pii: RA118.006237. doi: 10.1074/jbc.RA118.006237. PMID:30567740[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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