2q74: Difference between revisions

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[[Image:2q74.jpg|left|200px]]
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{{STRUCTURE_2q74|  PDB=2q74  |  SCENE=  }}
'''Mycobacterium tuberculosis SuhB'''


==Mycobacterium tuberculosis SuhB==
<StructureSection load='2q74' size='340' side='right'caption='[[2q74]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q74]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q74 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q74 OCA], [https://pdbe.org/2q74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q74 RCSB], [https://www.ebi.ac.uk/pdbsum/2q74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q74 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SUHB_MYCTU SUHB_MYCTU] Catalyzes the dephosphorylation of inositol 1-phosphate (I-1-P) to yield free myo-inositol, a key metabolite in mycobacteria. Is also able to hydrolyze a variety of polyol phosphates such as glucitol-6-phosphate, inositol 2-phosphate (I-2-P), glycerol-2-phosphate, and 2'-AMP, albeit with reduced efficiency.<ref>PMID:11914086</ref>
== 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/q7/2q74_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=2q74 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. RESULTS: We determined the crystal structure, to 2.6 A resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. CONCLUSION: The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.


==Overview==
Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+.,Brown AK, Meng G, Ghadbane H, Scott DJ, Dover LG, Nigou J, Besra GS, Futterer K BMC Struct Biol. 2007 Aug 28;7:55. PMID:17725819<ref>PMID:17725819</ref>
BACKGROUND: The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. RESULTS: We determined the crystal structure, to 2.6 A resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. CONCLUSION: The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2Q74 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q74 OCA].
</div>
<div class="pdbe-citations 2q74" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+., Brown AK, Meng G, Ghadbane H, Scott DJ, Dover LG, Nigou J, Besra GS, Futterer K, BMC Struct Biol. 2007 Aug 28;7:55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17725819 17725819]
*[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]]
[[Category: Inositol-phosphate phosphatase]]
== References ==
[[Category: Mycobacterium tuberculosis]]
<references/>
[[Category: Single protein]]
__TOC__
[[Category: Besra, G S.]]
</StructureSection>
[[Category: Brown, A K.]]
[[Category: Large Structures]]
[[Category: Futterer, K.]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Ghadbane, H.]]
[[Category: Besra GS]]
[[Category: Meng, G.]]
[[Category: Brown AK]]
[[Category: Alpha-beta-alpha-beta-alpha sandwich]]
[[Category: Futterer K]]
[[Category: Hydrolase]]
[[Category: Ghadbane H]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:28:08 2008''
[[Category: Meng G]]
Retrieved from "https://proteopedia.org/2q74"